Methods for treating, ameliorating or preventing infections using drug and vaccination combination treatment

ABSTRACT

In alternative embodiments, provided are methods for treating, ameliorating, decreasing the chances of having any adverse effects from, decreasing the severity of adverse effects from, or preventing an infection by administration of an antibiotic and/or an anti-viral drugs and a vaccine directed to a causative agent of the infection and/or an attenuated and/or a live, viable or infectious causative agent of the infection. In alternative embodiments, the infection is bacterial or viral. In alternative embodiments, the viral infection is a coronavirus infection such a Covid-19 infection. In alternative embodiments, methods as provide herein prevent or decrease the prevalence or severity of “vaccine breakthrough infections” after vaccination, where external mutants of COVID-19 infect patients in spite of the fact that they have undergone immunization, for example, to prevent a mutant or variant COVID-19 infection. In alternative embodiments, an antiviral combination administered in coordination with a vaccine comprises PF-07321332 or PAXLOVID™ and/or ritonavir, or ivermectin, doxycycline and a zinc or a zinc salt. In alternative embodiments, methods as provided herein are used to prevent in vivo mutations of such mutant infectious agent to enhance the efficacy of an administered vaccination; in other words, methods as provided herein are used to prevent in vivo replication of an acquired viral mutant or variant infectious agent, and thus also prevents ongoing mutations of the viral infectious agent because using the combination antiviral co-therapy where there is no replication of infectious agent and so there is no possible further mutation of the infectious agent.

RELATED APPLICATIONS

This U.S. Utility Patent application claims the benefit of priorityunder 35 U.S.C. § 119(e) of U.S. Provisional Application Serial No.(USSN) 63/186,660, filed May 10, 2021; U.S. Ser. No. 63/188,311, May 13,2021; U.S. Ser. No. 63/214,997, Jun. 25, 2021; USSN 63/223,427, Jul. 19,2021; U.S. Ser. No. 63/241,485 filed Sep. 7, 2021; U.S. Ser. No.63/253,813 filed Oct. 8, 2021; and, U.S. Ser. No. 63/273,069, filed Oct.28, 2021. The aforementioned applications are expressly incorporatedherein by reference in its entirety and for all purposes.

TECHNICAL FIELD

This invention generally relates to medicine and the medical treatmentof infections with vaccines, antibiotics and anti-viral drugs. Inalternative embodiments, provided are methods for treating,ameliorating, decreasing the chances of having any adverse effects from,decreasing the severity of adverse effects from, or preventing aninfection by administration of an antibiotic and/or an anti-viral drugsand a vaccine directed to a causative agent of the infection and/or aninactivated or attenuated causative agent of the infection, or a live,viable or infectious causative agent of the infection. In alternativeembodiments, the infection is bacterial, parasitic or viral. Inalternative embodiments, the viral infection is a coronavirus infectionsuch a Covid-19 or Covid-19 variant infection. In alternativeembodiments, methods as provided herein prevent or decrease theprevalence or severity of “vaccine breakthrough infections” aftervaccination, where mutants of the infection's causative agent developand infect patients in spite of the fact that they have undergoneimmunization, for example, to prevent a Covid-19 infection. Inalternative embodiments, methods as provided herein are used to preventin vivo mutations of an infectious agent to enhance to efficacy of anadministered vaccination; in other word, methods as provided herein areused to prevent in vivo replication of a viral infectious agent, andthus also prevents mutations of the viral infectious agent because wherethere is no replication of infectious agent there is no mutation ofinfectious agent. In alternative embodiments, methods comprisingadministration of a combination of an antiviral medication, drug ortreatment such as PF-07321332 or PAXLOVID™ and/or ritonavir and avaccine prevents acquisition of externally mutated viruses infecting thevaccinated person, as well as preventing replication in those possessingless effective neutralising antibodies to the mutants.

BACKGROUND

The process of immunization attempts to create immunity to preventacquisition of the new coronavirus or viruses. However, there is ongoingmutation occurring in the surrounding population because of ongoingreplication of viruses. Hence, “vaccine breakthrough” infections arebecoming reported, for example, see Hacisuleyman et al., New Eng J Med,Apr. 21, 2021. If the vaccine creates immunity to only the strains itwas created for, it may permit ‘reinfection’ with Covid-19 of a mutantstrain inhaled by the immunized person. This is termed “Vaccinebreakthrough’. Within the immunized person replication of an externalinfectious mutant can take place because the vaccine alone is inadequateto control the mutant replicating and the mutant strain may furthermutate in this seemingly safely immunized subject.

With COVID-19, there has been a rush into development of vaccines thatcould prevent the disease. However, the nature of this infection, beingan intracellular RNA type of virus, does not result in an easydevelopment of a vaccine. There are vaccines which work, for example,small pox, tetanus, polio, or measles, and there are conditions wherevaccines are of little use, for example, hepatitis C, humanimmunodeficiency virus (HIV) infection and tuberculosis (TB), and thenthere are vaccines which only give partial immunization and for a shortperiod of time, such as for example influenza virus immunization andmore recently malaria immunization attempts.

Currently used mRNA vaccines as well as non-mRNA vaccines aremanufactured by different companies such as Pfizer, AstraZeneca,Moderna, Johnson and Johnson (Janssen), Sputnik V, NovaVax, Sinovac,Sinopharm, Biological E, Valneva, EpiVac Corona, Convidiciae, Covaxinand others. All have been subject to various local side effects such asa swollen arm, systemic side effects such as fever, aches and pains,overwhelming feeling of doom, discomfort, profound tiredness and othersymptoms. A small percentage of patients develop thrombocytopenia andclotting which is reminiscent of disseminated intravascular coagulationas described by some, as well as neurologic, dermatologic, cardiac andother adverse effects.

The preventative success of mRNA vaccines has been reported to be up to90% or more. However, in real life experience data in some countries hasshown results of 50% to 90% efficacy. Some of these reduced efficacylevels may be due to mutants being present in that population. Unlessvaccine manufacturers can predict the development of specific mutations,which is virtually impossible, the vaccine market will always sufferfrom such reduced efficacy in various regions of the world.

Because of the ongoing mutations around the world of COVID-19, there aremultiple strains, including a current India strain, which has causedsuper-infections in patients who have been immunized, i.e., theso-called vaccine breakthrough phenomenon. The B.1.617 variant of theCovid-19, known more commonly as the double mutant strain, was firstdetected in India in October 2020. As the name suggests, the straininvolves two variants of the virus. The E484Q mutation hascharacteristics of a previously detected variant—the E484K—which wasseen in the fast-spreading Brazilian and South African variants, makingit highly transmissible. The L452R mutation, on the other hand, helpsthe virus evade the body's immune response. The double mutation strainwas subsequently named B.1.617

Yet it is clear that the virus had to replicate to mutate. Hence theadage “if it cannot replicate it cannot mutate”. Hence, one simplesolution to the problem of imperfect vaccine disease prevention is not abigger and better vaccine or multiple vaccinations because we will neverkeep up with the mutations. The best solution may well be prevention ofmutations. Yet it is clear that the virus had to replicate to mutate.And subsequently replicate in the immunized person. Hence the adage “ifit cannot replicate it cannot mutate”.

SUMMARY

In alternative embodiments, provided are methods for treating,ameliorating, decreasing the chances of having any adverse effects from,decreasing the severity of adverse effects from, or preventing aninfection, comprising administering to a subject or an individual inneed thereof, wherein optionally the individual in need thereof is ahuman or an animal:

-   -   (a) at least one antibiotic and/or anti-viral drug capable of        killing a causative agent of the infection, or completely or        partially inhibiting the ability of the causative agent of the        infection to replicate or become infectious or cause pathology        in the subject or the individual in need thereof; and,    -   (b) (i) at least one dose of a vaccine directed to the causative        agent of the infection upon entry into the vaccinated subject or        individual in need thereof,    -   wherein the vaccine is capable of initiating an immune response        in the individual that can substantially or partially kill or        neutralize a causative agent of the infection, or the vaccine        can completely, substantially or partially inhibit the ability        of the causative agent of the infection to replicate, or be        infectious, or cause pathology, in the subject or the individual        in need thereof, and/or    -   (ii) an inactivated or attenuated agent of the infection, or a        live, viable or infectious causative agent of the infection,        wherein optionally the live causative agent of the infection is        a completely or partially attenuated version of the causative        agent,    -   wherein at least one dosage of the at least one antibiotic        and/or anti-viral drug is administered 1, 2, 3, 4, 5, 6, 7, 8,        9, 10, 11, 12, 13 or 14 or more days before, or on the day of, a        first dose of the at least one of a plurality of dosages of the        vaccine is administered, or a dose of the inactivated,        attenuated, or the live, viable or infectious causative agent of        the infection.

In alternative embodiments, the causative agent of the infection is orcomprises a bacteria, protozoan or a virus, or the causative agent ofthe infection is or comprises the causative agent of:

-   -   a viral infection, optionally a coronavirus, a virus that causes        a common cold, an influenza virus (optionally an influenza A, B        or C), a hepatitis virus, a respiratory syncytial virus (RSV), a        Paramyxoviridae or measles virus, a Paramyxovirus or mumps        virus, a Herpes simplex virus (HSV), a Cytomegalovirus (CMV), a        Rubivirus or rubella virus, an Enterovirus, a viral meningitis,        a rhinovirus, a human immunodeficiency virus (HIV), a        varicella-zoster or chickenpox virus, an Orthopoxvirus or        variola or smallpox virus, an Epstein-Barr virus (EBV), an        Adenovirus, a Hantavirus, a Flaviviridae or Dengue virus, a Zika        virus, or a chikungunya virus infection,    -   a coronavirus infection, optionally a COVID-19 or a COVID-19        variant infection, or a Middle East respiratory syndrome virus        (MERS-CoV) infection;    -   malaria caused by a parasite of the genus Plasmodium        (optionally P. vivax, P. falciparum, P. malariae, P. ovale,        or P. knowlesi);    -   dengue fever or dengue shock syndrome caused by a virus of the        Flaviviridae family or a dengue virus;    -   a Flaviviridae family virus infection or a hepatitis or a        hepatocellular carcinoma associated with viral hepatitis caused        by a virus of the Flaviviridae family or a virus of the genus        Hepacivirus or Hepacivirus C virus or hepatitis C;    -   filariasis, leprosy or streptocerciasis or an infection caused        by a parasite of the superfamily Filarioidea (optionally Brugia        malayi, Brugia timori, Wuchereria bancrofti, Loa loa Mansonella        streptocerca, Mansonella ozzardi, or Mansonella perstans);    -   leprosy or an infection caused by a parasite of the genus        Mycobacterium (optionally M. leprae or M lepromatosis);    -   river blindness or onchocerciasis caused by a parasitic worm or        a parasite of the genus Onchocerca (optionally O. volvulus);    -   a hookworm or a roundworm infection caused by a parasite of the        genus Ancylostoma (optionally A. duodenale or A. ceylanicum) or        Necator (optionally N. americanus);    -   trichuriasis or a whipworm infection caused by a parasite of the        genus Trichuris (optionally T. trichiura); roundworm or an        Ascaris infection that is caused by Ascaris lumbricoides;    -   scabies or a mite-carried infection caused by the parasite of        the genus Sarcoptes (optionally S. scabiei);    -   typhus or an infection caused by a lice or a parasite of the        order Phthiraptera (optionally Pediculus humanus capitis);    -   enterobiasis or an infection caused by a pinworm or a parasite        of the genus Enterobius (optionally E. vermicularis); and/or    -   pulicosis or an infection caused by a flea or an insect of the        order Siphonaptera or of the genus Pulex (optionally P.        irritans).

In alternative embodiments, the virus is an influenza virus or acoronavirus, optionally a COVID-19 virus.

In alternative embodiments, the at least one antibiotic and/oranti-viral drug comprises: an avermectin class drug (optionallyivermectin) alone; a combination of an avermectin class drug and anantibiotic, or a combination of an ivermectin and an antibiotic or anantiviral drug or therapeutic, optionally a combination of an avermectinclass drug, an antibiotic and zinc or a zinc salt, or a combination ofivermectin and an antibiotic and zinc or a zinc salt.

In alternative embodiments, the avermectin class drug comprises:ivermectin (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin(optionally milbemectin, milbemycin oxime, moxidectin or nemadectin),doramectin (optionally DECTOMAX™), eprinomectin or abamectin. Inalternative embodiments, the avermectin class drug is administered witha synthetic nucleoside analog or derivative, or N4-hydroxycytidine, or aprodrug of N4-hydroxycytidine, optionally molnuvpiravir (Merck), orfavipiravir (also known as T-705 or AVIGAN™, or favilavir, ToyamaChemical, Fujifilm, Japan, or FABIFLU™, Glenmark Pharmaceuticals).

In alternative embodiments, the antibiotic comprises an antibacterialantibiotic or a macrolide drug,

-   -   wherein optionally the macrolide drug comprises azithromycin,        optionally dosaged at between about 50 mg to about 2000 mg per        dose or per day (optionally, ZITHROMAX™, or AZITHROCIN™,        optionally an oral extended- or delayed-release formulation of        azithromycin, or ZMAX™), clarithromycin (optionally, BIAXIN™),        erythromycin (optionally, ERYTHROCIN™), or fidaxomicin        (optionally, DIFICID™ or DIFICLIR™), troleandomycin (optionally,        TEKMISIN™), tylosin (optionally, TYLOCINE™ or TYLAN™),        solithromycin (optionally, SOLITHERA™), oleandomycin (or        SIGMAMYCINE™), midecamycin, roxithromycin, kitasamycin or        turimycin, josamycin, carbomycin or magnamycin, and/or        spiramycin,    -   and optionally the antibacterial antibiotic comprises a        tetracycline class drug, a glycylcycline or a fluorocycline        class drug, or an analogue thereof, and optionally the        tetracycline, glycylcycline or fluorocycline drug or analogue        thereof comprises or is: tetracycline or SUMYCIN™;        chlortetracycline or AUREOMYCIN™; oxytetracycline;        demeclocycline or DECLOMYCIN™, DECLOSTATIN™, LEDERMYCIN™,        BIOTERCICLIN™, DEGANOL™, DETECLO™, DETRAVIS™, MECICLIN™,        MEXOCINE™, CLORTETRIN™; lymecycline; meclocycline; metacycline;        minocycline or MINOCIN™; rolitetracycline; doxycycline, or        DORYX™, DOXYHEXA™, DOXYLIN™; tigecycline or TYGACIL™;        eravacycline or XERAVA™; sarecycline or SEYSARA™ omadacycline or        NUZYRA™; or any combination thereof.

In alternative embodiments, the at least one antibiotic and/oranti-viral drug comprises a combination of ivermectin and doxycycline(optionally DORYX™, DOXYHEXA™, DOXYLIN™), optionally a combination ofivermectin, doxycycline and zinc or a zinc salt.

In alternative embodiments, the at least one antibiotic and/oranti-viral drug comprises a combination of ivermectin and azithromycin(optionally, ZITHROMAX™, or AZITHROCIN™, optionally an oralextended-release formulation of azithromycin, or ZMAX™), optionally acombination of ivermectin, azithromycin and zinc or a zinc salt.

In alternative embodiments, the at least one antibiotic and/oranti-viral drug comprises a combination of hydroxychloroquine(optionally, PLAQUENIL™) and azithromycin (optionally, ZITHROMAX™, orAZITHROCIN™, optionally an oral extended-release formulation ofazithromycin, or ZMAX™), optionally a combination of hydroxychloroquine,azithromycin and zinc or a zinc salt.

In alternative embodiments, the at least one antibiotic and/oranti-viral drug further comprises administration of a vitamin,optionally vitamin D and/or vitamin C.

In alternative embodiments, the zinc comprises: zinc sulphate, zincacetate, zinc gluconate or zinc picolinate or a zinc salt.

In alternative embodiments, on the day of administration of, or at leastone day after the first dose of: (a) the attenuated and/or the live,viable or infectious causative agent of the infection, and/or (b) thevaccine, is given, the individual in need thereof is administered moreof the at least one antibiotic and/or anti-viral drug, or a differentcombination of an least one antibiotic and/or anti-viral drug, or adifferent dosage of the at least one antibiotic and/or anti-viral drug.

In alternative embodiments, the individual in need thereof isadministered more of the at least one antibiotic and/or anti-viral drug,or a different combination of an least one antibiotic and/or anti-viraldrug, or a different dosage of the at least one antibiotic and/oranti-viral drug on day zero (the day of administration), or day 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 after administration of the firstdosage of the vaccine and/or the attenuated and/or the live, viable orinfectious causative agent of the infection.

In alternative embodiments, a booster, or at least one second orfollow-up administration of: at least one dosage of a vaccine and/or anattenuated and/or a live, viable or infectious causative agent of theinfection, is given between about 1 week to one year (or between abouttwo weeks to 9 months, or between about three weeks to 8 months, orbetween about one month to 7 months, or about 3, 4, 5, or 6 months)after the first administration of the at least one vaccine and/or theattenuated and/or the live, viable or infectious causative agent of theinfection,

-   -   and optionally, wherein on day zero, or at least one day, or        about two days, after, administration of the second or        additional or booster dose of the vaccine, and/or the attenuated        and/or the live, viable or infectious causative agent of the        infection, is given, the individual in need thereof is        administered more of the at least one antibiotic and/or        anti-viral drug, or a different combination of an least one        antibiotic and/or anti-viral drug, or a different dosage of the        at least one antibiotic and/or anti-viral drug.

In alternative embodiments, the individual in need thereof isadministered more of the at least one antibiotic and/or anti-viral drug,or a different combination of an least one antibiotic and/or anti-viraldrug, or a different dosage of the at least one antibiotic and/oranti-viral drug on day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14after administration of the second or additional or booster dose of thevaccine and/or the attenuated and/or the live, viable or infectiouscausative agent of the infection.

In alternative embodiments, the at least one antibiotic and/oranti-viral drug is repeatedly administered about every 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13 or 14 or more days for one or several weeks(optionally, 2, 3, 4, 5, or 6 weeks) until plasma ivermectin isdetectable.

In alternative embodiments, the vaccine is: a nucleic acid-basedvaccine, optionally an RNA vaccine or a DNA vaccine; a peptide orpolypeptide-based vaccine; or, the vaccine comprises an inactivatedvirus.

In alternative embodiments, the anti-bacterial and/or anti-viral drug ordrug combination, or the attenuated and/or the live, viable orinfectious causative agent of the infection, or the vaccine, isadministered orally or by inhalation, or the the anti-bacterial and/oranti-viral drug or drug combination or the attenuated and/or the live,viable or infectious causative agent of the infection is administered byinclusion in a liquid (optionally to be administered as a drink or indrops such as nasal drops or in a mist), a tablet, a capsule, a gel, ageltab, a powder, a lozenge, an aerosol, spray, or mist formulation thatis inhaled or administered nasally or orally (optionally, by a puffer ora nebulizer), or is formulated in a liquid (optionally the liquid is asterile saline) solution which is ingested or gargled by the individualin need thereof.

In alternative embodiments, the attenuated and/or the live, viable orinfectious causative agent of the infection is administered in unitdosages of between about 10 to 50 trillion infectious units orparticles, or between about one infectious unit or particle to 10, 20 or30 billion infection units or particles.

In alternative embodiments, after the first administration of (a) theattenuated and/or the live, viable or infectious causative agent of theinfection, and/or (b) the vaccine, the IgM, IgG and/or IgA levels in theindividual in need thereof is tested and measured (qualitatively and/orquantitatively), and optionally if levels of the measured IgM, IgGand/or IgA are low, a second or additional dosage or administration ofthe (a) the attenuated and/or the live, viable or infectious causativeagent of the infection, and/or (b) the vaccine, is given,

-   -   and optionally levels of the measured IgM, IgG and/or IgA are        measured at between about 7 to 21 days, or at 14 and 20 days,        after the first administration.

In alternative embodiments, the individual in need thereof is a human oran animal, and optionally the animal is a domestic, farm or zoo animal.

In alternative embodiments, the methods comprise administering incoordination with (optionally before, at the time of and/or aftervaccination of and/or administration of the attenuated and/or the live,viable or infectious causative agent of the infection) theanti-microbial (optionally antiviral) vaccine and/or the attenuatedand/or the live, viable or infectious causative agent of the infection,a therapeutic combination of drugs or a single drug, an antisera or anantibody, a pharmaceutical dosage form, a drug delivery device, or aproduct of manufacture, comprising:

-   -   (a) a thiazolide class drug, optionally nitazoxanide (or        ALINIA™, NIZONIDE™) or tizoxanide (or        2-Hydroxy-N-(5-nitro-2-thiazolyl)benzamide);    -   (b) molnupiravir, optionally co-administered with and/or        formulated with an avermectin class drug (optionally        ivermectin), an antibiotic (optionally doxycycline or        azithromycin) and/or zinc, or co-administered with and/or        formulated with ivermectin, hydroxychloroquine, an antibiotic        (optionally doxycycline or azithromycin) and/or zinc;    -   (c) opaganib or YELIVA™, or opaganib or YELIVA™ and oral and/or        inhaled or aerosol chloroquine (or ARALEN™), chloroquine        phosphate, chloroquine diphosphate, amodiaquine (or AMDAQUINE™,        AMOBIN™) and/or hydroxychloroquine (optionally, PLAQUENIL™),        wherein optionally each or both of the opaganib and the        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        are in or formulated as a formulation for inhalation, for        example, formulated as an aerosol, spray, mist, liquid or        powder, or each or both are formulated for oral, intramuscular        or intravenous administration,    -   wherein optionally the opaganib is administered at a dosage of        QD (once a day), bid (twice a day) or tid (three times a day) at        a dosage of between about 100 to 600 mg per day or per dosage,        or at about 100, 200, 300, 400, 500 or 600 mg per day or per        dosage,    -   and optionally the opaganib, or YELIVA™ is also administered or        formulated with an antibiotic (optionally azithromycin or        doxycycline), ivermectin (optionally at 12 mg ivermectin,        optionally administered on days 1, 3, 6 and 8),        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc        (optionally zinc sulfate, optionally at (50 mg daily, or any        zinc salt);    -   (d) lopinavir, ritonavir (or NORVIR™) and oseltamivir        (optionally, TAMIFLU™), and/or zanamivir (or RELENZA™);    -   (e) lopinavir combined (formulated) with ritonavir (or NORVIR™),        or KALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or        LOPINAVIR™, and/or zanamivir (or RELENZA™), or lopinavir and        ritonavir separately formulated;    -   (f) lopinavir combined (formulated) with ritonavir (or NORVIR™)        (or KALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or        LOPINAVIR™), or lopinavir and ritonavir (or NORVIR™), and        oseltamivir (optionally, TAMIFLU™), and/or zanamivir (or        RELENZA™), optionally also with inhaled or aerosol formulations        or versions of chloroquine (or ARALEN™) amodiaquine (or        AMDAQUINE™, AMOBIN™), chloroquine phosphate, and/or oral        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        simultaneously;    -   (g) lopinavir, ritonavir (or NORVIR™), amodiaquine (or        AMDAQUINE™, AMOBIN™), chloroquine and oseltamivir (or TAMIFLU™);        wherein optionally the chloroquine comprises inhaled or aerosol        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        and/or oral chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) simultaneously;    -   (h) lopinavir and oseltamivir (optionally, TAMIFLU™), and/or        zanamivir (or RELENZA™);    -   (i) ritonavir (or NORVIR™) and oseltamivir (optionally,        TAMIFLU™), and/or zanamivir (or RELENZA™);    -   (j) remdesivir (optionally, GS-5734™, Gilead Sciences) alone, or        oseltamivir (optionally, TAMIFLU™) and remdesivir (optionally,        GS-5734™, Gilead Sciences), and optionally the remdesivir is an        oral formulation and/or an inhaled or aerosol remdesivir        formulation;    -   (k) oseltamivir (optionally, TAMIFLU™) and efavirenz        (optionally, SUSTIVA™), and/or zanamivir (or RELENZA™);    -   (l) oseltamivir (optionally, TAMIFLU™) and nevirapine (or the        combination efavirenz with emtricitabine and tenofovir, or        ATRIPLA™);    -   (m) oseltamivir (or TAMIFLU™) and amprenavir (optionally,        AGENERASE™);    -   (n) oseltamivir (optionally, TAMIFLU™) and nelfinavir        (optionally, VIRACEPT™);    -   (o) a thiazolide class drug, optionally nitazoxanide (optionally        ALINIA™ NIZONIDE™) or tizoxanide (or        2-Hydroxy-N-(5-nitro-2-thiazolyl)benzamide), with or in        combination with any of (a) to (hh), or any drug or drug        combination as provided herein, optionally a thiazolide class        drug, optionally nitazoxanide, with an avermectin class drug        such as ivermectin (optionally STROMECTOL™), moxidectin        (optionally CYDECTIN™, EQUEST™, QUEST™), selamectin (optionally        STRONGHOLD™), a milbemycin (optionally milbemectin, milbemycin        oxime, moxidectin or nemadectin), doramectin (optionally        DECTOMAX™), eprinomectin or abamectin; or a thiazolide class        drug (optionally, nitazoxanide or tizoxanide) and oseltamivir        (or TAMIFLU™),    -   and optionally the thiazolide class drug (optionally,        nitazoxanide or tizoxanide) is formulated or administered with        ribavirin or tribavirin (or COPEGUS™, REBETOL™, or VIRAZOLE™),        and an avermectin class drug such as ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin;    -   (p) plitidepsin (also known as dehydrodidemnin B), or APLIDIN™        (PharmaMar, S. A.);    -   (q) an inhibitor or S-phase kinase-associated protein 2 (SKP2),        or dioscin, or niclosamide, or NICLOCIDE™, FENASAL™, or        PHENASAL™;    -   (r) ribavirin or tribavirin (or COPEGUS™, REBETOL™, or        VIRAZOLE™) interferon beta 1b, or a combination of ribavirin and        interferon beta, or a combination of lopinavir and ritonavir (or        NORVIR™) and interferon-beta-1b;    -   (s) abacavir, acyclovir, or optionally ACICLOVIR™, adefovir,        amantadine, ampligen, amprenavir (optionally, AGENERASE™),        aprepitant, umifenovir (or ARBIDOL™), atazanavir, atripla,        balavir, baloxavir marboxil (XOFLUZA™) bepotastine, bevirimat,        bictegravir, a combination of bictegravir and emtricitabine and        tenofovir alafenamide (or BIKTARVY™), brilacidin, bivalirudin        (or BIVALITROBAN™), cidofovir, caspofungin, lamivudine and        zidovudine (optionally, COMBVIR™), cobicstat, colisitin,        cocaine, darunavir, delavirdine, descovy, didanosine, docosanol,        dolutegravir, ecoliever, edoxudine, efavirenz (optionally,        SUSTIVA™), elvitegravir, emtricitabine, enfuvirtide, entecavir,        epirubicin, epoprostenol, etravirine, famciclovir, fomivirsen,        fosamprenavi, foscarnet, fosfonet, galidesivir, ibacitabine,        icatibant, idoxuridine, ifenprodil, imiquimod, imunovir,        indinavir, inosine, an interferon (optionally interferon type I,        interferon type II and/or interferon type III), lamivudine (or        EPIVIR™, ZEFFIX™), lopinavir, loviride, ledipasvir, leronlimab,        maraviroc, methisazone, moroxydine, nelfinavir, nevirapine,        nexavir, nitazoxanide (optionally ALINIA™, NIZONIDE™), norvir, a        nucleoside analogue or derivative (optionally brincidofovir (or        TEMBEXA™), didanosine (or VIDEX™), favipiravir (also known as        T-705 or AVIGAN™, or favilavir, Toyama Chemical, Fujifilm,        Japan, or FABIFLU™, Glenmark Pharmaceuticals), vidarabine,        galidesivir (optionally, BCX4430, IMMUCILLIN-A™), remdesivir        (optionally, GS-5734™, Gilead Sciences), cytarabine,        gemcitabine, emtricitabine, lamivudine, zalcitabine, abacavir,        acyclovir, entecavir, stavudine, telbivudine, zidovudine,        idoxuridine and/or trifluridine or any combination thereof),        oseltamivir (or TAMIFLU™), peginterferon alfa-2a, penciclovir,        peramivir (optionally, RAPIVAB™), perfenazine, pleconaril,        plurifloxacin, podophyllotoxin, pyramidine, raltegravir,        rifampicin, ribavirin or tribavirin (or COPEGUS™, REBETOL™, or        VIRAZOLE™), rilpivirine, rimantadine, ritonavir (or NORVIR™)        saquinavir, sofosbuvir, stavudine, telaprevir, tegobuv,        tenofovir alafenamide, tenofovir disoproxil, tenofovir,        tipranavir, trifluridine, trizivir, tromantadine, truvada,        valaciclovir (optionally, VALTREX™), valganciclovir, valrubicin,        vapreotide, vicriviroc, vidarabine, viramidine, velpatasvir,        vivecon, zalcitabine, zanamivir (optionally, RELENZA™),        zidovudine, an immunosuppressive drug (optionally tocilizumab or        atlizumab, or ACTEMRA™, or ROACTEMRA™) or any combination        thereof;    -   (t) a mucolytic therapy or drug, optionally acetylcysteine,        ambroxol, bromhexine (or BISOLVON™), carbocisteine, erdosteine,        mecysteine or dornase alfa, or an expectorant, optionally        guaifenesin;    -   (u) a viral, or a coronavirus or a COVID-19, protease inhibitor,        optionally ASC09 (CAS registry no. 1000287-05-7) (Janssen        Research and Development, LLC), ritonavir (or NORVIR™) or ASC09        and ritonavir, or a JAK1/2 inhibitor (optionally baricitinib),        optionally compound 11r (University of Lubeck, Germany, see        optionally, Zhang et al J. Med Chem 2020, Feb. 11, 2020), or        darunavir, cobicistat or darunavir and cobicistat;    -   (v) an angiotensin-converting enzyme 2 (ACE2) inhibitor,        optionally to block the site of viral spike protein interaction        for anti-SARS-CoV-2 infection control;    -   (w) an anti-vascular endothelial growth factor (VEGF)        (optionally VEGF-A) drug or antibody, optionally bevacizumab;    -   (x) a protease inhibitor, optionally danoprevir, optionally a        serine protease inhibitor, optionally camostat or narlaprevir        (optionally ARLANSA™);    -   (y) anti-PD-1 checkpoint inhibitor, optionally camrelizumab;    -   (z) a compound or antibody capable of binding complement factor        C5 and blocking membrane attack complex formation, optionally        eculizumab;    -   (aa) a cathepsin inhibitor, optionally a cathepsin K, B or L        inhibitor, optionally relacatib;    -   (bb) thalidomide, or thalidomide and glucocorticoid (optionally        low-dose glucocorticoid), or and thalidomide and celecoxib;    -   (cc) an antibacterial antibiotic or a macrolide drug,    -   wherein optionally the macrolide drug comprises azithromycin,        optionally dosaged at between about 50 mg to about 2000 mg per        dose or per day (optionally, ZITHROMAX™, or AZITHROCIN™,        optionally an oral extended- or delayed-release formulation of        azithromycin, or ZMAX™), clarithromycin (optionally, BIAXIN™),        erythromycin (optionally, ERYTHROCIN™), or fidaxomicin        (optionally, DIFICID™ or DIFICLIR™), troleandomycin (optionally,        TEKMISIN™), tylosin (optionally, TYLOCINE™ or TYLAN™),        solithromycin (optionally, SOLITHERA™), oleandomycin (or        SIGMAMYCINE™), midecamycin, roxithromycin, kitasamycin or        turimycin, josamycin, carbomycin or magnamycin, and/or        spiramycin,    -   and optionally the antibacterial antibiotic comprises a        tetracycline class drug, a glycylcycline or a fluorocycline        class drug, or an analogue thereof, and optionally the        tetracycline, glycylcycline or fluorocycline drug or analogue        thereof comprises or is: tetracycline or SUMYCIN™;        chlortetracycline or AUREOMYCIN™; oxytetracycline;        demeclocycline or DECLOMYCIN™, DECLOSTATIN™, LEDERMYCIN™,        BIOTERCICLIN™, DEGANOL™, DETECLO™, DETRAVIS™, MECICLIN™,        MEXOCINE™, CLORTETRIN™; lymecycline; meclocycline; metacycline;        minocycline or MINOCIN™; rolitetracycline; doxycycline, or        DORYX™, DOXYHEXA™, DOXYLIN™; tigecycline or TYGACIL™;        eravacycline or XERAVA™; sarecycline or SEYSARA™; omadacycline        or NUZYRA™; or any combination thereof,    -   and optionally the antibacterial antibiotic or macrolide drug,        optionally azithromycin (or ZMAX™), is administered in        combination with, and/or is combined with, chloroquine (or        ARALEN™), amodiaquine (or AMDAQUINE™, AMOBIN™), chloroquine        phosphate, chloroquine diphosphate and/or hydroxychloroquine        (optionally, PLAQUENIL™), and the combination is administered        commencing on the first, second, third, fourth, fifth, sixth,        seventh, eighth, ninth and/or tenth day of therapy, or is        administered for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or up to 20 or        more days, or for between about 1 to 21 days or longer, or is        administered until within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or up to        20 or more days of ending the therapy for treating, preventing,        ameliorating, slowing the progress of, decreasing the severity        of or preventing the coronavirus infection,    -   and optionally the chloroquine (or ARALEN™), chloroquine        phosphate, amodiaquine (or AMDAQUINE™, AMOBIN™), chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        is administered the entire length of the treatment but the        azithromycin, optionally dosaged at between about 50 mg to about        2000 mg per dose or per day (optionally, ZITHROMAX™, or        AZITHROCIN™, optionally an oral extended-release formulation of        azithromycin, or ZMAX™) administration is halted or ceased after        two, three, four, five or six days after treatment is commenced,        and optionally the azithromycin administration is replaced by a        tetracycline class drug, and optionally the tetracycline class        drug comprises doxycycline, or DORYX™, DOXYHEXA™, DOXYLIN™        administration,    -   and optionally the antibacterial antibiotic, optionally        azithromycin (optionally, ZITHROMAX™, or AZITHROCIN™, optionally        dosaged at between about 50 mg to about 2000 mg per dose or per        day,    -   and optionally an oral extended-release formulation of        azithromycin, or ZMAX™), is administered or formulated with an        avermectin class drug such as ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin, and/or cholecalciferol (vitamin D3) or calcifediol,    -   and optionally the antibacterial antibiotic comprises an        antimycobacterial drug, and optionally the antimycobacterial        drug comprises clofazimine (optionally LAMPRENE™);    -   (dd) an avermectin class drug such as ivermectin (optionally        STROMECTOL™, SOOLANTRA™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin, optionally dosaged and/or administered at about 5        microgram/kg to about 1 gram (g) per day, optionally formulated        or administered at about 1 to 10, 12, 15, 20, 30, 40, 50, 60,        70, 80, 100, 120, 140, 160, 180, 200, 220 or 240 mg per day, or        between about 1 to 240 mg per day, or between about 3 to 240 mg        per day,    -   optionally formulated or administered with an antibiotic        (optionally azithromycin, minocycline, amoxicillin, niclosamide,        nitazoxanide, hydroxychloroquine or doxycycline, and optionally        the doxycycline is at between about 25 to 600 mg per dose or per        day, or at about 100 mg per dose or per day, and optionally the        azithromycin is at between about 50 mg to 2000 mg per dose or        per day), optionally as a single or a divided dose, and        optionally formulated and administered as an inhalant or a mist        (optionally using a nebulizer, nasal spray or equivalent),        optionally formulated as an aerosol, spray, mist, liquid or        powder, optionally formulated as an aerosol, spray, mist, liquid        or powder,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is formulated with and/or administered with        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        with or without zinc (optionally a zinc sulphate, acetate,        gluconate or picolinate or any zinc salt), and optionally this        combination is administered weekly, or every two week, or one        every 5 to 28 days, as a prophylactic,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is administered alone in the morning (AM), and an        antibiotic (optionally doxycycline) and/or a chloroquine        (optionally, ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        is administered in the afternoon and/or evening,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is administered alone for 1, 2, 3, 4, 5, 6, 7, 8,        9, 10 or up to 20 or more days, followed by administration of an        antibiotic (optionally doxycycline) for a corresponding period        of days, and optionally repeating the cycle of dosaging,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is formulated or administered with:        -   (i) at least one antibiotic (wherein optionally the            antibiotic is doxycycline(optionally, DORYX™, DOXYHEXA™,            DOXYLIN™) (optionally formulated or administered at a dosage            of between about 25 mg to 600 mg per dose or per day), or            azithromycin (optionally, ZITHROMAX™, or AZITHROCIN™,            optionally dosaged at between about 50 mg to about 2000 mg            per dose or per day, optionally an oral extended-release            formulation of azithromycin, or ZMAX™) (optionally            formulated or administered at a dosage of between an about            50 mg to 2000 mg);        -   (ii) chloroquine (or ARALEN™), chloroquine phosphate,            chloroquine diphosphate and/or hydroxychloroquine            (optionally, PLAQUENIL™) (optionally formulated or            administered at a dosage of between an about 10 mg to 2000            mg per day);        -   (iii) a zinc (optionally a zinc sulphate, acetate, gluconate            or picolinate or any zinc salt) optionally formulated or            administered at a dosage of between about 1 mg to 250 mg;            and/or        -   (iv) at least one vitamin, and optionally the at least one            vitamin comprises: vitamin C optionally formulated or            administered at a dosage of between about 500 to 5000            units (U) per dose, and/or Vitamin D (or cholecalciferol)            optionally formulated or administered at a dosage of between            about 3,000 to 100,000 units per day, or between about            10,000 to 50,000 units a day,        -   and optionally the avermectin class drug such as ivermectin            (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,            EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a            milbemycin (optionally milbemectin, milbemycin oxime,            moxidectin or nemadectin), doramectin (optionally            DECTOMAX™), eprinomectin or abamectin is administered or            formulated alone or in combination with any of the above (i)            to (iv) (for example, at least one antibiotic, chloroquine            (or ARALEN™) chloroquine phosphate, chloroquine diphosphate            and/or hydroxychloroquine (optionally, PLAQUENIL™), zinc or            any zinc salt and/or at least one vitamin are formulated            (and administered) as oral formulations (for example, as            tablets, capsules, powders, gels or geltabs), injectable            formulations, powders (for example, for inhalation or for            addition to an ingestible liquid) or liquids (for example,            for ingestion, infusion or injection);    -   (ee) chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) alone or with (or formulated with) or in combination        with any of (a) to (bb), or chloroquine, chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) and oseltamivir (or TAMIFLU™);    -   (ff) chloroquine (optionally, ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) alone or with:        -   (i) an avermectin class drug such as ivermectin (optionally            STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,            QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin            (optionally milbemectin, milbemycin oxime, moxidectin or            nemadectin), doramectin (optionally DECTOMAX™), eprinomectin            or abamectin, optionally at a dosage of between about 3 to            340 mg per day, or about 6 mg to 60 mg, or about 10 mg to 80            mg dosages, or about 12 to 50 mg dosages;        -   (ii) vitamin D, vitamin D2 (or ergocalciferol), vitamin D3            (or cholecalciferol) optionally at a dosage of between about            3,000 to 100,000 units per day, or between about 10,000 to            50,000 units a day, and/or        -   (iii) with (i) and (ii) and zinc (optionally a zinc            sulphate, acetate, gluconate or picolinate or any zinc salt)            optionally at a dosage of between about 1 mg to 250 mg,            or (iv) the combination of (iii) also with a tetracycline            class drug, wherein optionally the tetracycline class drug            comprises doxycycline, or DORYX™, DOXYHEXA™, DOXYLIN™,            optionally dosages at between about 25 mg to 600 mg per day            or per dose, optionally between about 100 mg to 500 mg, or a            between about 200 mg to 400 mg per dose or per day;    -   (gg) colchicine, or COLCRYS™, MITIGARE™, optionally administered        or dosaged at between about 0.5 mg to 20 mg, or about 1 mg to 15        mg, or about 3 mg to 10 mg, or about 4 mg to 6 mg, per day for a        period of between about 7 and 21 days, or about 14 days, and        optionally also administered or formulated with an antibiotic        (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily);    -   (hh) a corticosteroid or glucocorticoid class drug such as        ciclesonide (or ALVESCO™, OMNARIS™, OMNIAIR™, ZETONNA™ or        ALVESCO™) budesonide (optionally RHINOCORT™ or PULMICORT™),        prednisolone (or ORAPRED™), methyl-prednisolone, prednisone (or        DELTASONE™ or ORASONE™) or hydrocortisone (or CORTEF™), or a        selective estrogen receptor modulator (SERM), or toremifene (or        FARESTON™), or clomifene or clomiphene (or CLOMID™, SEROPHENE™),        wherein optionally the corticosteroid or glucocorticoid class        drug (optionally ciclesonide) is inhaled;    -   and optionally the corticosteroid class drug (for example        budesonide) is administered by inhalation, for example, in a        nebulized form, for example, between about 1 mg to 12 mg per day        of budesonide is administered by inhalation, or between about 6        to 80 mg per day of prednisolone is administered orally, or        between about 6 to 100 mg per day of prednisone is administered        orally, or between about 30 to 400 mg per day of hydrocortisone        is administered orally,    -   and optionally the corticosteroid class drug is formulated as a        powder or for administration in an inhaler or by nasal spray, or        for rectal administration,    -   and optionally the corticosteroid class drug (for example,        budesonide) is administered together with or in combination with        10 mg to 80 mg, an antibiotic (optionally azithromycin or a        tetracycline class drug,    -   wherein optionally the tetracycline class drug comprises        doxycycline, or DORYX™, DOXYHEXA™, DOXYLIN™), zinc or any zinc        salt and/or a vitamin (optionally vitamin D or calcifediol, D2        (or ergocalciferol), D3 (or cholecalciferol), C, E, B12, B6);    -   (ii) an anti-androgen drug, and optionally the anti-androgen        drug is bicalutamide, optionally CASODEX™, or dutasteride (or        AVODART™),        -   and optionally the anti-androgen drug is a nonsteroidal            anti-androgen (NSAA) or an androgen receptor (AR)            antagonist, and optionally the NSAA or AR antagonist            comprises proxalutamide (or its developmental name GT-0918)            (Suzhou Kintor Pharmaceuticals, Inc., a subsidiary of Kintor            Pharmaceutical Limited), or flutamide (or niftolide, or            EULEXIN™), or bicalutamide (or CASODEX™) or enzalutamide (or            XTANDI™),        -   and optionally the anti-androgen drug comprises a            5α-reductase inhibitor, and optionally the 5α-reductase            inhibitor comprises finasteride (or PROSCAR™, PROPECIA™, or            FINIDE™)        -   and optionally the anti-androgen drug, or NSAA, or            proxalutamide or bicalutamide, is administered together with            or in combination with an avermectin class drug such as            ivermectin (optionally STROMECTOL™), moxidectin (optionally            CYDECTIN™, EQUEST™, QUEST™), selamectin (optionally            STRONGHOLD™), a milbemycin (optionally milbemectin,            milbemycin oxime, moxidectin or nemadectin), doramectin            (optionally DECTOMAX™), eprinomectin or abamectin;        -   and optionally the anti-androgen drug, or NSAA, or            bicalutamide, proxalutamide, flutamide or niftolide,            bicalutamide, enzalutamide or dutasteride, is administered            at dosages of about 50 to 100 mg optionally administered            once, twice (BID), three times (TID) or four times a day, or            is administered at dosages of about 50 to 100 mg per day,        -   and optionally the anti-androgen drug, or NSAA, or            bicalutamide, proxalutamide, flutamide or niftolide,            bicalutamide, enzalutamide or dutasteride, is administered            with an avermectin class drug, or ivermectin, optionally            also administered with hydroxychloroquine, zinc and/or a            vitamin (optionally vitamin D (optionally vitamin D2, or            ergocalciferol, or Vitamin D3 or cholecalciferol, optionally            administered at about 1000 to 4000 ugm/day) or vitamin C, B            or A;    -   and optionally bicalutamide is administered together with or in        combination with an avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin,    -   and optionally bicalutamide is administered together with or in        combination with an avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin;    -   (jj) a hydrocortisone or cortisol (optionally CORTEF™,        SOLUCORTEF™), optionally hydrocortisone sodium succinate or        hydrocortisone acetate or dexamethasone (optionally DEXTENZA™,        OZURDEX™, NEOFORDEX™);    -   (kk) an alpha-ketoamide (α-ketoamide), wherein optionally the        alpha-ketoamide is a structure as described by Zhang et al, J.        Med. Chem. 2020, 63, 9, 4562-4578, or Meng et al Chem.        Sci. (2019) vol. 10, pg 5156 (optionally the structure KAM-2),    -   and optionally the alpha-ketoamide is formulated or administered        as an inhalant or a powder or mist, and optionally formulated or        administered with (optionally as an inhalant): an avermectin        class drug such as ivermectin (optionally STROMECTOL™),        moxidectin (optionally CYDECTIN™, EQUEST™, QUEST™), selamectin        (optionally STRONGHOLD™), a milbemycin (optionally milbemectin,        milbemycin oxime, moxidectin or nemadectin), doramectin        (optionally DECTOMAX™), eprinomectin or abamectin; an antibiotic        (optionally azithromycin or a tetracycline class drug, wherein        optionally the tetracycline class drug comprises doxycycline, or        DORYX™, DOXYHEXA™, DOXYLIN™); chloroquine (or ARALEN™),        chloroquine phosphate, chloroquine diphosphate and/or        hydroxychloroquine (optionally, PLAQUENIL™); zinc or any zinc        salt; remdesivir (optionally, GS-5734™, Gilead Sciences);        oseltamivir (or TAMIFLU™); and/or, hydrocortisone; or, any        combination thereof;    -   (ll) a compound, drug or formulation that decreases stomach acid        production or decreases stomach pH, wherein optionally the        compound, drug or formulation comprises famotidine, or PEPCID™,        and optionally the famotidine is administered at a dosage of        between about 10 to 60 mg per day, or between about 20 to 40 mg        per day, and optionally the famotidine is administered is        administered with: an avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin, and/or a tetracycline tetracycline class drug, and        optionally the tetracycline class drug comprises doxycycline, or        DORYX™, DOXYHEXA™, DOXYLIN™;    -   (mm) a dendrimer, optionally astodrimer sodium (Starpharma,        Melbourne, Australia);    -   (nn) an antihistamine class drug such as azelastine, or        ASTELIN™, OPTIVAR™, ALLERGODIL™, brompheniramine, fexofenadine        or ALLEGRA™ pheniramine or AVIL™, or chlorpheniramine;    -   (oo) a selective serotonin reuptake inhibitor (SSRI) class drug,        optionally fluvoxamine, or LUVOX™, FAVERIN™, FLUVOXIN™;    -   (pp) a nicotinic antagonist, a dopamine agonist or a        noncompetitive N-Methyl-d-aspartic acid or N-Methyl-d-aspartate        (NMDA) antagonist, wherein optionally the nicotinic antagonist,        dopamine agonist or noncompetitive NMDA antagonist is        1-adamantylamine or amantadine, or GOCOVRI™, SYMADINE™,        SYMMETREL™, optionally administered or dosaged at between about        50 mg to 150 mg, or about 100 mg, per day for a period of        between about 7 and 21 days, or about 14 days, and optionally        the nicotinic antagonist, dopamine agonist or noncompetitive        NMDA antagonist is also administered or formulated with an        antibiotic (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily),        and optionally the amantadine is formulated or administered at        100 mg per day for the first two days of treatment, which        optionally can then be elevated to 100 mg twice daily,        optionally for the next 10 days;    -   (qq) an immunosuppressive drug, wherein optionally the        immunosuppressive drug comprises tocilizumab or atlizumab, or        ACTEMRA™, or ROACTEMRA™, or a calcineurin inhibitor (CNI),        wherein the CNI comprises ciclosporin (or cyclosporine or        cyclosporin), or NEORAL™, or SANDIMMUNE™, or tacrolimus, or        PROTOPIC™, or PROGRAF™, and optionally the immunosuppressive        drug is also administered or formulated with an antibiotic        (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily),    -   and optionally the calcineurin inhibitor (CNI), wherein the CNI        comprises ciclosporin (or cyclosporine or cyclosporin) is        formulated combination of CNI (optionally cyclosporine) at a        dose of 3 mg/kg (180 mg daily) together with 12 mg ivermectin        once, and optionally also plus zinc 50 mg base and doxycycline        100 mg bid, optionally all for 10 days;    -   (rr) a protein kinase inhibitor, wherein optionally the protein        kinase inhibitor is a p38 mitogen-activated protein kinase        inhibitor, or ralimetinib, and optionally the protein kinase        inhibitor is also administered or formulated with an antibiotic        (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily);    -   (ss) an anti-inflammatory therapy or at least one        anti-inflammatory therapy drug, wherein optionally the        anti-inflammatory therapy or drug comprises: a sphingosine        kinase-2 (SK2) selective inhibitor (optionally, opaganib        (optionally, YELIVA™), sirolimus, a JAK1/2/TYK2 inhibitor        (optionally ruxolitinib), an anti-CD47 mAb (optionally        meplazumab), a cyclooxygenase (COX) (optionally, COX2)        inhibitor, a glucocorticoid (optionally a synthetic        glucocorticoid, hydrocortisone, dexamethasone (or DEXTENZA™,        OZURDEX™, or NEOFORDEX™) or cortisol, or CORTEF™) or ciclesonide        (or ALVESCO™, OMNARIS™, OMNIAIR™, ZETONNA™ or ALVESCO™),        plitidepsin or dehydrodidemnin B, or APLIDIN™, or a nonsteroidal        anti-inflammatory drug (NSAID), wherein optionally the NSAID        comprises indomethacin (or indomethacin) or INDOCID™ or        INDOCIN™, or naproxen, or NAPROSYN™ or ALEVE™, or a        cyclooxygenase inhibitor, or a COX-1 or an COX-2 inhibitor, or        aspirin, or ibuprofen or ADVIL™, MOTRIN™ or NUROFEN™, or        celecoxib or CELEBREX™, or parecoxib or DYNASTAT™, or etoricoxib        or ARCOXIA™,    -   and optionally the anti-inflammatory therapy or        anti-inflammatory therapy drug is also administered or        formulated with an antibiotic (optionally azithromycin or        doxycycline), ivermectin, hydroxychloroquine (optionally,        PLAQUENIL™) and/or zinc or any zinc salt (optionally zinc        sulfate, optionally at (50 mg daily),    -   and optionally opaganib, or YELIVA™, or opaganib, or YELIVA™        administered or formulated together with an oral and/or inhaled        or aerosol chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™)    -   and optionally the opaganib or YELIVA™ is formulated or        administered at a dosage of QD (once a day), bid (twice a day)        or tid (three times a day) at a dosage of between about 100 to        600 mg per day or per dosage, or at about 100, 200, 300, 400,        500 or 600 mg per day or per dosage,    -   and optionally the opaganib, or YELIVA™ is also administered or        formulated with an antibiotic (optionally azithromycin or        doxycycline), ivermectin (optionally at 12 mg ivermectin,        optionally administered on days 1, 3, 6 and 8),        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily);    -   (tt) a calcium channel blocker, or verapamil (or ISOPTIN™,        CALAN™), or a voltage gated potassium (KCNH2) channel or a        voltage gated calcium channel (CACNA2D2) blocker, or amiodarone        (or CORDARONE™, NEXTERONE™);    -   (uu) suramin, or ANTRYPOL™, BAYER 305™, or GERMANIN™    -   (vv) a peroxisome proliferator-activated receptor (PPAR)        agonist, wherein optionally the PPAR agonist comprises        fenofibrate, or TRICOR™, FENOBRAT™, FENOGLIDE™, or LIPOFEN™, or        a combination of fenofibrate and simvastatin, or CHOLIB™,        optionally the PPAR agonist comprises a combination of        fenofibrate and pravastatin, or PRAVAFENIX™, or the PPAR agonist        comprises bezafibrate, or BEZALIP™, or combination of        bezafibrate and chenodeoxycholic acid, or HEPACONDA™, or        aluminium clofibrate, or alfibrate, or ciprofibrate, or        clinofibrate or LIPOCLIN™, or clofibrate or ATROMID-S™, or        clofibride, or gemfibrozil or LOPID™, or ronifibrate, or        simfibrate or CHOLESOLVIN™, or any combination thereof,    -   (ww) a synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or a prodrug of N4-hydroxycytidine,        optionally molnuvpiravir (Merck), or favipiravir (also known as        T-705 or AVIGAN™, or favilavir, Toyama Chemical, Fujifilm,        Japan, or FABIFLU™, Glenmark Pharmaceuticals),    -   wherein the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is given as between        about 10 mg to 3 gm per dose, or between about 10 mg to 3 gm per        day, or can be dosed either as a single dose or given one, two,        three or four times a day, or is administered at 200 to 800 mg        twice daily, or 200, 400, 600 or 800 mg twice daily, or at 200        to 800 mg three times a day, or at 200, 400, 600 or 800 mg three        times a day, or is administered at 200 to 800 mg three times a        day for between about 2 to 15 days, or for about 2, 3, 4, 5, 6,        7, 8, 9, 10, 11 or 12 days, and optionally when combined with        other drugs a lower dosage is used, optionally administered at        100 or 200 mg three times a day for between about 5 to 15 days,        or for about 7, 8, 9, 10, 11 or 12 days,    -   and optionally the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is administered with an        avermectin class drug (optionally ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin),    -   and optionally the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is administered with an        avermectin class drug (optionally ivermectin) with an        antibiotic, and optionally the antibiotic comprises        azithromycin, minocycline, amoxicillin, niclosamide,        nitazoxanide, hydroxychloroquine or doxycycline), and optionally        the synthetic nucleoside analog or derivative, avermectin class        drug, and antibiotic are administered together or as separate        formulations, and optionally are administered every one, two,        three, four or five weeks for between about one month and one        year or more;    -   and optionally molnuvpiravir, ivermectin and hydroxychloroquine        are administered together or as separate formulations, and        optionally are administered every one, two, three, four or five        weeks for between about one month and one year or more;    -   and optionally the synthetic nucleoside analog or derivative        (optionally N4-hydroxycytidine, or the prodrug of        N4-hydroxycytidine, optionally molnuvpiravir or favipiravir),        and antibiotic (optionally doxycycline or hydroxychloroquine) is        administered with zinc (optionally a zinc sulphate, acetate,        gluconate or picolinate, or zinc oxide nanoparticles, optionally        at a dosage of between about 1 mg to 250 mg, or about 50 mg per        day) and/or a vitamin, optionally vitamin C or D),    -   and optionally the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is administered with an        antibiotic (optionally the antibiotic comprises azithromycin,        minocycline, amoxicillin, niclosamide, nitazoxanide,        hydroxychloroquine or doxycycline), optionally also administered        with zinc (optionally a zinc sulphate, acetate, gluconate or        picolinate, or zinc oxide nanoparticles, optionally at a dosage        of between about 1 mg to 250 mg, or about 50 mg per day) and/or        a vitamin, optionally vitamin C or D,    -   and optionally any of these combinations is administered very 2,        3, 4, 5, 6, 7, 8, 9 or 10 or more days for between about 1 month        and one year or more;    -   (xx) an antisera or an antibody or antibody or vaccine therapy        for treating, preventing or ameliorating a microbial or a viral        infection (optionally a coronavirus infection, optionally a        COVID-19 infection) or a microbial infection (optionally a        protozoan, helminthiasis, insect and/or parasitic infection),        and optionally the antibody comprises a monoclonal antibody, and        optionally the monoclonal antibody comprises sotrovimab        (GlaxoSmithKline and Vir Biotechnology), or casirivimab,        imdevimab or casirivimab and imdevimab (REGEN-COV™) (Regeneron),        or bamlanivimab oretesevimab or bamlanivimab and etesevimab        (Junshi Biosciences), or tocilizumab or ACTEMRA™ or ROACTEMRA™        (Hoffmann-La Roche), and optionally the vaccine comprises        tozinamera or COMIRNATY™ (Pfizer), or elasomeran or SPIKEVAX™        (Moderna), or SPUTNIK V™ or Gam-COVID-Vac (Gamaleya Research        Institute), or AZD1222 or COVISHIELD™ or VAXZEVRIA™        (Oxford-AstraZeneca),    -   and optionally the antibody or antibody therapy comprises or is        contained in a convalescent sera or plasma, and/or    -   (yy) any combination of (a) to (xx),    -   and optionally any one or several or all of (a) to (yy) with an        (or formulated with or formulated as an) inhaled or aerosol        formulation such as a powder or a mist or aerosol, and/or        formulated with or formulated as an oral, intramuscular (IM) or        intravenous (IV) formulation, wherein optionally both the        inhaled (or aerosol) and the oral, IV and/or IM formulations are        administered simultaneously or sequentially,    -   and optionally the inhaled or aerosol formulation comprises        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        and/or oral chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) administered simultaneously or overlapping,    -   and optionally the inhaled or aerosol formulation comprises an        avermectin class drug such as ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin,

and optionally any one or several or all of (a) to (yy), or anytherapeutic combination of drugs or a drug, or a pharmaceutical dosageform as provided herein, are administered orally, intramuscularly,subcutaneously, topically, by use of an enema, intravaginally, orintravenously, or administration is by subcutaneous administration,sublingual administration, inhalation or by aerosol (optionally byinhalation of a liquid, an aerosol, a spray, a mist or a powder), byabsorbable patch, by use of an implant, or by use of an enema or asuppository.

In alternative embodiments, the anti-viral drug or medication, oranti-microbial drug, is or comprises: molnupiravir, efavirenz(optionally, SUSTIVA™), tenofovir, emtricitabine and tenofovir,nevirapine (or the combination efavirenz with emtricitabine andtenofovir, or ATRIPLA™), amprenavir (optionally, AGENERASE™), nelfinavir(optionally, VIRACEPT™) and/or remdesivir (optionally, GS-5734™, GileadSciences), a viral RNA-dependent RNA polymerase inhibitor, optionallygalidesivir,

-   -   and optionally the anti-viral drug or medication is or comprises        an anti-retroviral drug or drug combination, and optionally the        anti-retroviral drug or drug combination comprises: darunavir        and cobicistat (optionally, REZOLSTA™ or PREZCOBIX™); atazanavir        (or REYATAZ™) and cobicistat (or EVOTAZ™); a nucleoside analog        reverse-transcriptase inhibitor (NRTI) (optionally abacavir, or        ZIAGEN™), lamivudine and dolutegravir (TRIUMEQ™); tenofovir (or        disoproxil or emtricitabine) and elvitegravir and cobicistat        (optionally, STRIBILD™); tenofovir (or disoproxil or        emtricitabine) and elvitegravir and cobicistat (COMPLERA™ or        EVIPLERA™); molnupiravir, efavirenz (optionally, SUSTIVA™),        emtricitabine and tenofovir (ATRIPLA); lamivudine, nevirapine        and stavudine (optionally, TRIOMUNE™); atazanavir (or REYATAZ™)        and cobicistat (optionally, EVOTAZ™); lamivudine and raltegravir        (optionally, DUTREBIS™); lamivudine and dolutegravir (or        DOVATO™); doravirine, lamivudine and tenofovir (optionally,        DELSTRIGO™); or lamivudine, zidovudine and nevirapine        (optionally, CUOVIR-N™);    -   and optionally the additional anti-viral drug or medication, or        anti-microbial drug, is formulated with the chloroquine        (optionally, ARALEN™), chloroquine phosphate, chloroquine        diphosphate, hydroxychloroquine (optionally, PLAQUENIL™),        lopinavir, ritonavir (or NORVIR™) and/or oseltamivir or is        formulated separately from the chloroquine (optionally,        ARALEN™), chloroquine phosphate, chloroquine diphosphate,        hydroxychloroquine (optionally, PLAQUENIL™), lopinavir,        ritonavir (or NORVIR™) and/or oseltamivir,    -   and optionally the anti-viral drug or medication, or        anti-microbial drug, or palliative agent comprises or further        comprises: magnesium (Mg, optionally administer        intravenously (IV) to maintain a blood concentration of between        about 2.0 and 2.4 mmol/1); zinc or any zinc salt (optionally a        zinc sulphate, acetate, gluconate or picolinate, optionally        administered at about 75 to 100 mg/day or at a dosage of between        about 1 mg to 250 mg); at least one vitamin, wherein optionally        the at least one vitamin comprises vitamin K, vitamin D or        calcifediol (optionally D2 (or ergocalciferol) or Vitamin D3 or        cholecalciferol), optionally administered at about 1000 to 4000        ugm/day), vitamin B6 (or pyridoxine), vitamin B12, vitamin E,        and/or vitamin C (optionally administered at 500 mg bid); a        flavonoid, plant flavonol or quercetin optionally administered        at between about 250 to 500 mg bid; atorvastatin, or LIPITOR™,        SORTIS™ (optionally administered at between about 40 mg/day to        80 mg/day); or, melatonin, or CIRCADIN™, SLENYTO™ (optionally        between about 6 to 12 mg a day, optionally, at night), any of        which are optionally given enterally or parenterally.

In alternative embodiments, provided are kits comprising a vaccineand/or an attenuated and/or live causative agent of infection, and atleast one antibiotic and/or anti-viral drug capable of killing acausative agent of the infection, or completely or partially inhibitingthe ability of the causative agent of the infection to replicate orbecome infectious or cause pathology in an individual, as describedherein or used in any method as provided herein, wherein optionally thekit comprises instructions for practicing a method as provided herein.

In alternative embodiments of methods and kits as provided herein, the

-   -   (i)        1R,2S,5S)-N-[(1S)-1-cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl]-3-[(2S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide,        or a compound having the following structure and molecular        weight:

-   -   or stereoisomer, or enantiomer, or deuterated version thereof,        and    -   (ii) ritonavir,    -   are formulated together, or separately, and optionally are        formulated together or separately in or as a liquid (optionally        to be administered as a drink or in drops, optionally as nasal        drops or in a mist), a tablet, a capsule, a gel, a geltab, a        powder, a lozenge, an aerosol or spray.

In alternative embodiments of methods and kits as provided herein, theanti-viral drug combination is formulated in or as a pharmaceuticaldosage form, optionally formulated to be administered orally,intramuscularly, subcutaneously, topically, by use of an enema,intravaginally, or intravenously, or formulated for subcutaneousadministration, sublingual administration, inhalation or by aerosol(optionally by inhalation of a liquid, an aerosol, a spray, a mist or apowder), by absorbable patch, by use of an implant, or by use of anenema or a suppository.

In alternative embodiments of methods and kits as provided herein, the

-   -   (a)        1R,2S,5S)-N-[(1S)-1-cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl]-3-[(2S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide,        or a compound having the following structure and molecular        weight:

-   -   or stereoisomer, or enantiomer, or deuterated version thereof,        and/or    -   (b) ritonavir,    -   is or are administered:    -   (a) at a dosage of QD (once a day), bid (twice a day) or tid        (three times a day) at a dosage of between about 100 to 600 mg        per day or per dosage, or at about 100, 200, 300, 400, 500 or        600 mg per day or per dosage, or    -   (b) at a dosage of between about 10 mg to 3 gm per dose, or        between about 10 mg to 3 gm per day, or 12 mg or 3 mg/kg orally        twice daily, or 125 mg orally twice daily or 520 mg/130 mg        solution twice per day (optionally administered with efavirenz,        fosamprenavir, nelfinavir, or nevirapine), or    -   (c) is dosed either as a single dose or given one, two, three or        four times a day, or    -   (d) at 200 to 800 mg twice daily, or 200, 400, 600 or 800 mg        twice daily, or at 200 to 800 mg three times a day, or at 200,        400, 600 or 800 mg three times a day, or is administered at 200        to 800 mg three times a day for between about 2 to 15 days, or        for about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 days,    -   (e) for pediatric patients dosage at 16 mg or 4 mg/kg orally        twice daily, or    -   (f) when combined with other drugs a lower dosage, optionally        administered at 100 or 200 mg three times a day for between        about 5 to 15 days, or for about 7, 8, 9, 10, 11 or 12 days.

The details of one or more exemplary embodiments of the invention areset forth in the description below. Other features, objects, andadvantages of the invention will be apparent from the description, andfrom the claims.

All publications, patents, patent applications cited herein are herebyexpressly incorporated by reference in their entireties for allpurposes.

DETAILED DESCRIPTION

In alternative embodiments, provided are methods for treating,ameliorating, decreasing the chances of having any adverse effects from,decreasing the severity of adverse effects from, or preventing aninfection in an individual in need thereof, including humans andanimals, by administration of an antibiotic and/or an anti-viral drugsand a vaccine directed to a causative agent of the infection, and/or aninactivated or attenuated causative agent of the infection, or the live,viable or infectious causative agent of the infection. In alternativeembodiments, the infection (or causative agent of the infection) isparasitic, bacterial or viral. In alternative embodiments, the viralinfection is a coronavirus infection such a Covid-19 infection.

In alternative embodiments, methods as provide herein prevent ordecrease the prevalence or severity of “vaccine breakthrough infections”after vaccination, where external mutants of the infection's causativeagent develop and infect or re-infect patients in spite of the fact thatthey have undergone immunization, for example, to prevent a Covid-19infection. Thus, in alternative embodiments, methods as provided hereincomprise combining an effective anti-microbial (for example anti-viral)treatment (for example, a drug or a mixture of drugs or othertherapeutics) with an anti-microbial vaccine to prevent in vivomutations (and thus also prevent a vaccine breakthrough infection) of aninfectious agent such as virus, for example, a coronavirus such asCOVID-19 or variant thereof.

In alternative embodiments, methods as provide herein provide a solutionto the problem of imperfect vaccine disease prevention, where a biggerand/or better vaccine or multiple vaccinations are ineffective becausescience will never keep up with the continuing viral mutations. Inalternative embodiments, methods as provide herein prevent replicationof newly-inhaled mutants in the already vaccinated or ‘about to bevaccinated’ population.

In alternative embodiments, methods as provide herein comprise an addedanti-replication method of treatment in addition to vaccination toprotect the immunized population from mutants entering, replicating, andfurther mutating in the immunized population. In alternativeembodiments, methods as provide herein prevent replication and thusprevent an ongoing viral mutation, a method utilized by the mutant toescape neutralizing antibodies and destruction. No replication, nomutation.

In alternative embodiments, methods as provide herein comprise combiningan effective anti-microbial (for example anti-viral) treatment (forexample, a drug or a mixture of drugs or other therapeutics) with ananti-microbial vaccine such as a DNA vaccine such as an adenovirus-basedvaccine, an mRNA vaccine, a peptide-based vaccine, an inactivatedpathogen-based vaccine, and/or an vaccine manufactured by:

-   -   Sanofi (optionally VAT00002 or VAT00008),    -   GlaxoSmithKline,    -   Takeda Pharmaceutical (optionally TAK-019),    -   Pfizer (optionally tozinamera or COMIRNATY™),    -   Moderna (optionally elasomeran or SPIKEVAX™)    -   Novavax (optionally vaccine to SARS VLPs S protein and influenza        M1 protein),    -   CanSino Biologics,    -   Inovio,    -   Sinovac,    -   BioNTech,    -   Johnson and Johnson,    -   Valneva (France) and Dynavax Technologies (optionally VLA2001        and VLA2101),    -   Sinopharm (or China National Pharmaceutical Group Corporation),    -   Emergent BioSolutions (optionally human polyclonal hyperimmune        serum with antibodies to SARS-CoV-2),    -   Bharat Biotech (optionally COVAXIN®),

The Rockefeller University (optionally vaccine toMVA S alone, or MVA-Sprime and Ad5-S boost),

-   -   Helmholtz Centre for Infection Research; Technical University        Munich; German Center for Environmental Health (optionally        vaccine to NC protein add-mixed with MALP-2 by intranasal route        and boosting with MVA-NC by intramuscular route),    -   University of Manitoba; University of Pennsylvania School of        Medicine; Southern Research Institute; Fox Chase Cancer        Institute (optionally vaccine to Heterologous Adenoviral prime        boost AdHu5 s AdC7-nS),    -   University of North Carolina at Chapel Hill, USA (optionally        vaccine to VEEV replicon particles expressing the SARS-CoV S),    -   National Institute of Infectious Diseases, Japan (optionally        vaccine to recombinant D1 expressing S protein),    -   Beijing Institute of Genomics, China (optionally vaccine to        Recombinant trunctuated S—N fusion protein),    -   Saitama Medical University; Josai University; Nippon Oil and Fat        Corporation; National Institute of Infectious Diseases, Japan        (optionally vaccine to recombinant peptide N223 on liposomes),    -   Chinese Center for Disease Control and Prevention; Canadian        Science Centre for Human and Animal Health (optionally vaccine        to Recombinant TM-truncated S protein),    -   HKU-Pasteur Research Centre; The University of Hong Kong;        National Institutes of Health; Centers for Disease (optionally        vaccine to Trimeric Spike protein),    -   Sun Yat-sen University, China (optionally vaccine to SARS S DNA        prime and HLAA*0201 restricted peptides boost vaccine),    -   State Key Laboratory of Virology; Graduate University of Chinese        Academy of Sciences (optionally vaccine to or as a 3a DNA        vaccine),    -   Institute of ImmunoBiology, Shanghai Medical College of Fudan        University, China (optionally vaccine to DNA prime—protein        S437-459 and M1-20),    -   CNB-CSIC; University of Iowa (optionally vaccine to rSARSCoV-E),    -   International Vaccine Institute (IVI) (optionally vaccine to        recombinant adenovirus expressing truncated S protein (rADV-S)),    -   University Health Network, Canada, and United States Center for        Disease Control and Prevention (CDC) (optionally vaccine to        recombinant measles virus spike protein),    -   Institut Pasteur (optionally vaccine to MV-SARS recombinant        measles virus vaccine expressing SARS CoV antigen),    -   Baylor College Medicine; Sabin; New York Blood Center (NYBC);        University of Texas Medical Branch (UTMB); Walter Reed Army        Institute of    -   Research (WRAIR); National Institute of Allergy and Infectious        Diseases (NIAID) (optionally vaccine to receptor binding domain        (RBD) of the SARS-CoV spike (S) protein),    -   Vaxine Pty Ltd, Australia (optionally vaccine to SARS        recombinant spike protein plus delta inulin),    -   Gamaleya Research Institute (optionally SPUTNIK V™ or        Gam-COVID-Vac), and/or    -   Oxford-AstraZeneca (optionally AZD1222 or COVISHIELD™ or        VAXZEVRIA™)    -   and others, including anti-COVID-19 vaccines.

Hence, methods as provided herein that combine antibiotic,anti-parasitic and/or anti-viral treatment with an inactivated orattenuated causative agent of an infection, or a vaccine or a live,viable or infectious causative agent of the infection (for example, alive or attenuated virus) administration, can treat, ameliorate orprevent a vaccine-breakthrough infection, as well as eradicating theinfection if present pre-vaccination enhance protection and eradicateinfection.

In alternative embodiments, methods as provide herein compriseadministering in coordination with (for example, before, during and/orafter) an anti-causative agent vaccination, or an anti-viralvaccination, and/or the inactivated or attenuated causative agent of theinfection, or the live, viable or infectious causative agent of theinfection (such as a live or attenuated virus) administration, any oneor combination of anti-viral, anti-parasitic or anti-bacterialtherapies, for example, one or more anti-COVID-19 infection medicationsor drugs, including for example, the drug ivermectin, or the combinationof ivermectin and an antibiotic with anti-viral properties such asdoxycycline or azithromycin, for example the combination of ivermectinand doxycycline or azithromycin, or the combination ivermectin anddoxycycline or azithromycin and zinc or any zinc salt (an anti-viralmineral, for example, and anti-COVID-19 mineral), which optionally alsocan be administered in conjunction or coordination with a vitamin orvitamins such as vitamin D and/or vitamin C.

In alternative embodiments, a drug combination administered incoordination with a vaccine and/or the inactivated or attenuatedcausative agent of the infection, or the live, viable or infectiouscausative agent of the infection (optionally a live or attenuated virus)administration comprises the commencement, optionally orally or byinhalation, of the antiviral combination before, or just before, and/orthe day (day zero) the vaccine and/or the inactivated or attenuatedcausative agent of the infection, or the live, viable or infectiouscausative agent of the infection (such as a live or attenuated virus)administration is given. For example, in alternative embodiments, thepatient (or individual in need thereof) is given a pre-vaccine drug oranti-viral treatment for between about 1 to 10 days, or between about 2to 21 days, depending on dosing and conditions. If the patient isalready infected but asymptomatic, because of this pre-vaccination (orpre-administration of the attenuated and/or the live infectiouscausative agent) treatment the patient will be free, or substantiallyfree, of the infection but not yet endowed with complete or partialimmunity. In other words, because of this pre-vaccination treatmentthere will be no virus, or substantially no virus, to replicate in vivoafter the anti-viral treatment. After administration of theanti-microbial drug or treatment (optionally, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13 or 14 or more days after a first anti-microbial drug ortreatment is first administered) the vaccine is given (depending on thetype of vaccine, this may be the first of a two or three injectionprocess). In alternative embodiments, after the first dose of thevaccine or the inactivated or attenuated causative agent of theinfection, or the live, viable or infectious causative agent of theinfection is given, the patient is treated at day 14 (or, optionally, onday 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14) with an antibioticor antiviral, for example, with a single preventative ivermectin andantibiotic drug combination (for example, using an antibiotic withanti-viral activity such as doxycycline or azithromycin), or ivermectinand doxycycline drug combination, or ivermectin and doxycycline and zincdrug combination, or ivermectin and azithromycin and zinc or any zincsalt, or any of these combinations with additional drugs or agent oradjuncts such as one or more vitamins, for example, vitamin B, C and/orD. In alternative embodiments, the drug combination administration isrepeated every 14 days (or, optionally, every 1, 2, 3, 4, 5, 6, 7, 8, 9,11, 12, 13 or 14 or more days) for several weeks until plasma ivermectinis detectable over the 14 days. In alternative embodiments, later, thedrug combination administration is repeated every 1, 2, 3, 4, 5 or 6weeks or more.

In alternative embodiments, a second dose of the vaccine and/or theinactivated or attenuated causative agent of the infection, or the live,viable or infectious causative agent of the infection, and optionallysubsequent boosters, are carried out between the intermittent (forexample, every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or up to 28days) anti-microbial (for example, anti-viral) doses.

In alternative embodiments, combining vaccine or the inactivated orattenuated causative agent of the infection, or the live, viable orinfectious causative agent of the infection with initial thenintermittent anti-microbial (for example, anti-viral) administrations asprovided herein achieves:

-   -   virtual 100%, or substantial (for example, 95% or more)        infectious agent (for example, COVID-19) abolition or in vivo        clearance, which can be achieved by the anti-microbial (for        example, anti-viral) pre-vaccination treatment arm of methods as        provided herein;    -   prolonged immunity, which can be achieved by administration of        combined vaccine and intermittent anti-microbial (for example,        anti-viral) treatments as provided herein;    -   lack of novel virus replication in the patient, which can be        achieved by the anti-microbial (for example, anti-viral)        pre-vaccination treatment arm of methods as provided herein;    -   no in vivo infectious agent (for example, virus) mutation in        treated patients, as there is no or substantially no (for        example, 90% to 99% reduction in) replication;    -   no ‘Long Covid Syndrome’, because if there is no infectious        agent (or substantially no infectious agent) remaining in the        patient in vivo, then can be no “Long Covid Syndrome”;    -   no or minimal hospitalization, and no or substantially decreased        number of deaths from Covid-19, because if there is no active in        vivo infection there can be no progression to morbidity or        mortality;    -   inability or substantial decrease in risk for patients treated        using the combination methods as provided herein catch or be        re-infected with any strain nor any mutant strain, where        patients administered methods as provided herein are induced to        have combined immunity (by administration of a vaccine) and an        anti-viral response induced by administration of a drug or drugs        which are viral mutant agonists;    -   eradication of primary viral (for example, COVID-19) infection,        because patients administered methods as provided herein receive        anti-microbial (for example, anti-viral) treatment at the        beginning of therapy; and/or,    -   ideal long-term preventative therapy for the elderly with        senescent immunity by supporting waning antibody levels in the        elderly patient with anti-microbial (for example, anti-viral)        treatment as provided herein; and also in embodiments where        ivermectin is administered, having the added benefit of rosacea        improvement and prevention of scabies in aged-care facilities.

Increasing the dose of the intermittent ivermectin combination increasesits anti-Covid-19 preventative power. In alternative embodiments, thedose is raised from between about 12 mg to about 36 mg, about 48 mg orabout 60 mg, or the dose is raised progressively to 120 mg with few ifany adverse effects. This will create a more prolonged circulatinglevel. This is expected to be close to 100% at 4 weeks, but whencombined with the vaccine could well prevent for up to 6 weeks or more.Hence, creating the possibility of reducing dosing to ×7/year. Given theuse of accompanying anti-viral drugs, even if the vaccine results inlower circulation of neutralizing antibody levels and so immunity, therisk of vaccine breakthrough infection will be minimal if at allpossible. Hence, this combination of anti-viral treatment together withthe vaccine would be ideal therapy for prevention of infection in theelderly population with senescent immune systems.

In alternative embodiments, any vaccine will benefit from practicingmethods as provided herein, particularly the mRNA vaccines, which willbenefit profoundly when combined with an effective anti-viral treatment.

In alternative embodiments, methods as provided herein comprise 1 to 10days of treatment with an ivermectin-based (or ivermectin-comprising)combination, followed by (the first dose of) vaccination, and then every1, 2, 3, 4, 5, 6 or 7 days, and later every 8, 9, 10, 11, 12, 13 or 14days (for example, every 7 days, then every 14 days), and later to 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 or 28 days (for example,every 7 days, then every 14 days, and later every 28 days), administer ahigher dose of ivermectin, for example, 60 mg ivermectin for 4 weekstogether with zinc or a zinc salt, doxycycline, vitamin D and vitamin Cor other appropriate combinations. As long as one continues theanti-viral treatment based on the 60 mg ivermectin regimen, a vaccinatedpatient has both circulating antibodies for many months and cannot catchmutated virus (for example, COVID-19 agents), and therefore “vaccinebreakthrough” will be prevented or substantially decreased and superinfection with mutants will be prevented or substantially decreased.

In alternative embodiments, methods as provided herein, including forexample the ivermectin, zinc or a zinc salt and doxycycline andoptionally also an adjunct therapy (such as for example administering avitamin such as vitamin C or D) is mutant agnostic. In alternativeembodiments, because methods as provided herein, including for examplethe ivermectin combination therapy, functions and works using adifferent mechanism by prevention of replication within a cell, nomutants can affect its activity as has been shown by us in clinicalpractice in California, United States. Hence, the combination of ananti-viral with a vaccine as provided herein may be the best method ofterminating the Covid-19 pandemic.

In alternative embodiments, the vaccination or the inactivated orattenuated causative agent of the infection, or the live, viable orinfectious causative agent of the infection administration may need tobe repeated, for example, repeated at 6 or 12 month (or between about 1(monthly) to 12 month) intervals, but it is of no great importancewhether it is 6 months or 12 months because the second arm or thetherapy as provided herein, the anti-viral arm, is on board to preventany further infection and therefore any further mutation in vivo in thepatient.

In alternative embodiments, even if a mutant or variant strain becomesthe predominant viral agent in a community in the future necessitatingthat the vaccine and/or the inactivated or attenuated causative agent ofthe infection, or the live, viable or infectious causative agent of theinfection be adjusted (or changed) to take in (be specific for) that newmutant or variant strain, the drug combination as provided herein, forexample, the ivermectin, zinc or a zinc salt and doxycycline plusadjunct treatment, can remain the same as it is mutant agnostic. Hence,any vaccine produced by any institution can be supplemented with ananti-viral combination such that no individuals will catch any viralstrains once the individual has begun this program (commenced receivingtreatment regimens as provided herein.

The concept of ‘redundancy’ of treatment is significant here; inmedicine, redundant treatment is one where the medication carries extrapower to cure the condition. In the event that the treatment had to beterminated early (for example, due to an allergy developing) thebuilt-in redundancy still delivers near (substantially) 100% curebecause it was designed to carry extra power. Hence, the combination ofthe anti-viral treatment and vaccination as provided herein carries ahigh level of redundancy and thus can achieve a close to 100% successrate (or a substantially completely successfully cure rate).

Although alternative embodiments of methods as provided herein are bestsuited to prevent and treat a virus such as a coronavirus such as aCovid-19 infection, alternative embodiments have multiple otherapplications. For example, in alternative embodiments, with appropriateantivirals methods as provided herein are used to prevent influenzainfections. In alternative embodiments, provided are methods comprisinga treatment regimen of an influenza (or other viral) vaccine followedlater by antiviral agents intermittently in once a week, 2 weekly, 3weekly, 4 weekly or less frequently spaced intervals to preventinfluenza mutants from re-infecting de novo susceptible elderly patientswith senescent immune system where influenza infection causes the mostmortality. Other exemplary antiviral combinations administeredpracticing methods as provided herein comprise use ofhydroxychloroquine, for example, hydroxychloroquine, azithromycin andzinc or a zinc salt.

In alternative embodiments, provided are methods comprising a treatmentregimen for treating: dengue fever, Zika, HIV, hepatitis C, Eboladisease, SARS, MERS, polio, measles, chickenpox and other viral orretro-viral infections. Where current immunizations may not beadequately effective, the follow-on with intermittent antiviral therapyas provide by methods as provided herein gives extra power for the poorimmune response combined with antivirals to have enough redundancy tomake it clinically effective.

In alternative embodiments, provided are methods comprising use ofantiviral compounds used singly or in multiple combinations, forexample, antiviral compounds are administered singly or in multiplecombinations, for example, before, at the time of vaccination, and/orafter vaccination:

For example, in alternative embodiments, methods provided hereincomprise administering in coordination with (optionally before, at thetime of vaccination, and/or after vaccination of) an anti-microbialvaccine a single drug or a therapeutic combination of drugs, or a singledrug, a pharmaceutical dosage form, a drug delivery device, or a productof manufacture, or the methods can comprise use of: one, two or moreclasses of antiviral drugs used against influenza, such as: M2 proteininhibitors (for example, amantadine and rimantadine); neuraminidaseinhibitors (for example, oseltamivir, zanamivir, peramivir andlaninamivir); favipiravir (also known as T-705 or AVIGAN™, or favilavir,Toyama Chemical, Fujifilm, Japan, or FABIFLU™ Glenmark Pharmaceuticals);a 5- to 6-membered heterocyclic ring such as benzene, naphthalene,furan, benzofuran, pyrrole, pyridine, pyrazole, imidazole,benzimidazole, triazole, tetrazole, oxazole, oxadiazole, 1,3,5-triazine,thiazole, thiophene, benzothiophene, pyrazine, pyridazine, pyrimidine,indole, purine, quinoline or isoquinoline; amantadine; rimantadine;oseltamivir; zanamivir; peramivir; laninamivir; laninamivir octanoatehydrate; arbidol; ribavirin; stachyflin; ingavirin; fludase; aniclosamide compound; an emricasan compound; nitazoxanide; tizoxanide;and/or a compound selected from consisting of teriflunomide,hydroxocobalamin, ensulizole, tenonitrozole, isoliquiritigenin,nitazoxanide, febuxostat, leflunomide, fidofludimus SB-366791, emodin,diphenyl isophthalate, benzoylpas, fenobam, indobufen,2-(2H-Benzotriazol-2-yl)-4-methylphenol, tiaprofenic acid, flufenamicacid, vitamin B12, cinanserin, 5-nitro-2-(3-phenylpropylamino)benzoicacid, veliflapon, thiabendazole, SIB 1893, anethole trithione,naringenin, phenazopyridine, fanetizole, terazosin, diacerein, CAY10505,hesperetin, suprofen, ketorolac tromethamine, piperine, pirarubicin,piraxostat, albendazole oxide, tyrphostin AG 494, genistin, fenbufen,apatinib, RITA, BF-170 hydrochloride, OSI-930, tribromsalan, pifexole,formononetin, ebselen, tranilast, benzylparaben,2-Ethoxylethyl-p-methoxycinnamate, baicalein, nemorubicin, rutaecarpine,2-Methyl-6-(phenylethynyl)pyridine (MPEP), 5,7-dihydroxyflavone, vitaminB12, pipofezine, flurbiprofen axetil, 2-Amino-6-nitrobenzothiazole,nalachite green oxalate, enfenamic acid, fenaminosulf, AS-252424,phenserine, epalrestat, alizarin, dalcetrapib, SN-38, echinomycin,(S)-(+)-camptothecin, BI-2536, 10-hydroxycamptothecin, topotecan,delanzomib, volasertib, ispinesib, paclitaxel, FK-506, emetine, AVN-944,digoxin, vincristine, idarubicin, thapsigargin, lexibulin, ixazomib,cephalomannine, mitoxantrone, MLN-2238, demecolcine, vinorelbine,bardoxolone methyl, cycloheximide, actinomycin D, AZD-7762, PF-184,CHIR-124, cyanein, triptolide, KX-01, PF-477736, epirubicin,mycophenolate (mycophenolic acid), daunorubicin, PIK-75, vindesine,torin-2, floxuridine, Go-6976, OSU-03012, and a prodrug, metabolite, orderivative of any of the foregoing.

In alternative embodiments the following compound (or its isomer, orstereoisomer, or enantiomer, or deuterated version, or bioisostere) isused singly or in various combinations (for example, formulated with, oradministered separately) with other drug such as anti-viral drugsbefore, during or after vaccination or administration of a causativeagent of infection:(1R,2S,5S)-N-[(1S)-1-cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl]-3-[(2S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamideadministered orally or by inhalation (or nasally), for example, asliquid, solid, powder, mist or spray, which can target a protease (suchas the 3CL protease in COVID-19) and optionally has the followingstructure and molecular weight:

This protease inhibitor (PF-07321332, or PAXLOVID™) may be used alonebefore and after the vaccination and/or administration of the attenuatedcausative agent of infection, optionally administered with ritonavir (orNORVIR™) or lopinavir, or with any of the numerous antiviral agents asprovided herein.

In alternative embodiments the following compounds (or their isomers, orstereoisomers, or enantiomer, or bioisostere) can be used singly or invarious combinations:

These compounds (PF-07304814 and/or PF-00835231) (or its isomer, orstereoisomer, or enantiomer, or deuterated version, or bioisostere) maybe used alone before and after the vaccination and/or administration ofthe attenuated causative agent of infection, optionally administeredwith ritonavir (or NORVIR™) or lopinavir, or with any of the numerousantiviral agents as provided herein.

In alternative embodiments, the PF-07321332 (or PAXLOVID™) and ritonavir(or NORVIR™) or lopinavir combination; or the PF-07304814 and/orPF-00835231 and ritonavir (or NORVIR™) or lopinavir combination; or theKALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or LOPINAVIR™ and/orzanamivir (or RELENZA™) combination; is administered separately, ortogether (for example, formulated together) as a tablet, gel, geltab orcapsule, as a powder, in a liquid, in a mist or a spray, or as alozenge. In alternative embodiments, the PF-07321332 (or PAXLOVID™) andritonavir (or NORVIR™) or lopinavir combination; or the PF-07304814and/or PF-00835231 and ritonavir (or NORVIR™) or lopinavir combination;or the KALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or LOPINAVIR™and/or zanamivir (or RELENZA™) combination; is administered before, atthe same time as, and/or after the vaccination.

In alternative embodiments, the PF-07321332 (or PAXLOVID™) and ritonavir(or NORVIR™) or lopinavir combination; or the PF-07304814 and/orPF-00835231 and ritonavir (or NORVIR™) or lopinavir combination; or theKALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or LOPINAVIR™ and/orzanamivir (or RELENZA™) combination; is administered 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13 or 14 or more days before, and/or on the day of,a first dose of the at least one of a plurality of dosages of thevaccine is administered, or a dose of the inactivated, attenuated, orthe live, viable or infectious causative agent of the infection isadministered.

In alternative embodiments, the PF-07321332 (or PAXLOVID™) and ritonavir(or NORVIR™) or lopinavir combination; or the PF-07304814 and/orPF-00835231 and ritonavir (or NORVIR™) or lopinavir combination; or theKALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or LOPINAVIR™ and/orzanamivir (or RELENZA™) combination; is administered 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13 or 14 or more days after a first dose of the atleast one of a plurality of dosages of the vaccine is administered, or adose of the inactivated, attenuated, or the live, viable or infectiouscausative agent of the infection is administered.

In alternative embodiments, the PF-07321332 (or PAXLOVID™) and ritonavir(or NORVIR™) or lopinavir combination; or the PF-07304814 and/orPF-00835231 and ritonavir (or NORVIR™) or lopinavir combination; or theKALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or LOPINAVIR™ and/orzanamivir (or RELENZA™) combination; is administered both before andafter a first dose of the at least one of a plurality of dosages of thevaccine is administered, or a dose of the inactivated, attenuated, orthe live, viable or infectious causative agent of the infection isadministered. Another agent which can be used singly or in combinationbefore and accompanying vaccination is 2-deoxy-D-Glucose (2-DG).

In alternative embodiments, methods as provided herein comprise (orfurther comprise) administering in coordination with (optionally before,at the time of vaccination, and/or after vaccination of) ananti-microbial vaccine (or a dose of the inactivated, attenuated, or thelive, viable or infectious causative agent of the infection) atherapeutic combination of drugs or a single drug, a pharmaceuticaldosage form, a drug delivery device, or a product of manufacture,comprising:

-   -   (a) a thiazolide class drug, optionally nitazoxanide (or        ALINIA™, NIZONIDE™) or tizoxanide (or        2-Hydroxy-N-(5-nitro-2-thiazolyl)benzamide);    -   (b) molnupiravir, optionally co-administered with and/or        formulated with an avermectin class drug (optionally        ivermectin), an antibiotic (optionally doxycycline or        azithromycin) and/or zinc, or co-administered with and/or        formulated with ivermectin, hydroxychloroquine, an antibiotic        (optionally doxycycline or azithromycin) and/or zinc; (c)        opaganib or YELIVA™, or opaganib or YELIVA™ and oral and/or        inhaled or aerosol chloroquine (or ARALEN™), chloroquine        phosphate, chloroquine diphosphate, amodiaquine (or AMDAQUINE™,        AMOBIN™) and/or hydroxychloroquine (optionally, PLAQUENIL™),        wherein optionally each or both of the opaganib and the        chloroquine (or ARALEN™) chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        are in or formulated as a formulation for inhalation, for        example, formulated as an aerosol, spray, mist, liquid or        powder, or each or both are formulated for oral, intramuscular        or intravenous administration,    -   wherein optionally the opaganib is administered at a dosage of        QD (once a day), bid (twice a day) or tid (three times a day) at        a dosage of between about 100 to 600 mg per day or per dosage,        or at about 100, 200, 300, 400, 500 or 600 mg per day or per        dosage,    -   and optionally the opaganib, or YELIVA™ is also administered or        formulated with an antibiotic (optionally azithromycin or        doxycycline), ivermectin (optionally at 12 mg ivermectin,        optionally administered on days 1, 3, 6 and 8),        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc        (optionally zinc sulfate, optionally at (50 mg daily, or any        zinc salt);    -   (d) lopinavir, ritonavir (or NORVIR™) and oseltamivir        (optionally, TAMIFLU™), and/or zanamivir (or RELENZA™);    -   (e) lopinavir combined (formulated) with ritonavir (or NORVIR™),        or KALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or        LOPINAVIR™, and/or zanamivir (or RELENZA™), or lopinavir and        ritonavir separately formulated;    -   (f) lopinavir combined (formulated) with ritonavir (or NORVIR™)        (or KALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or        LOPINAVIR™), or lopinavir and ritonavir (or NORVIR™), and        oseltamivir (optionally, TAMIFLU™), and/or zanamivir (or        RELENZA™), optionally also with inhaled or aerosol formulations        or versions of chloroquine (or ARALEN™) amodiaquine (or        AMDAQUINE™, AMOBIN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        and/or oral chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) simultaneously;    -   (g) lopinavir, ritonavir (or NORVIR™), amodiaquine (or        AMDAQUINE™, AMOBIN™), chloroquine and oseltamivir (or TAMIFLU™);        wherein optionally the chloroquine comprises inhaled or aerosol        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        and/or oral chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) simultaneously;    -   (H) lopinavir and oseltamivir (optionally, TAMIFLU™), and/or        zanamivir (or RELENZA™);    -   (i) ritonavir (or NORVIR™) and oseltamivir (optionally,        TAMIFLU™), and/or zanamivir (or RELENZA™);    -   (j) remdesivir (optionally, GS-5734™, Gilead Sciences) alone, or        oseltamivir (optionally, TAMIFLU™) and remdesivir (optionally,        GS-5734™, Gilead Sciences), and optionally the remdesivir is an        oral formulation and/or an inhaled or aerosol remdesivir        formulation;    -   (k) oseltamivir (optionally, TAMIFLU™) and efavirenz        (optionally, SUSTIVA™), and/or zanamivir (or RELENZA™);    -   (l) oseltamivir (optionally, TAMIFLU™) and nevirapine (or the        combination efavirenz with emtricitabine and tenofovir, or        ATRIPLA™);    -   (m) oseltamivir (or TAMIFLU™) and amprenavir (optionally,        AGENERASE™);    -   (n) oseltamivir (optionally, TAMIFLU™) and nelfinavir        (optionally, VIRACEPT™);    -   (o) a thiazolide class drug, optionally nitazoxanide (optionally        ALINIA™ NIZONIDE™) or tizoxanide (or        2-Hydroxy-N-(5-nitro-2-thiazolyl)benzamide), with or in        combination with any of (a) to (nn), or any drug or drug        combination as provided herein, optionally a thiazolide class        drug, optionally nitazoxanide, with an avermectin class drug        such as ivermectin (optionally STROMECTOL™), moxidectin        (optionally CYDECTIN™, EQUEST™, QUEST™), selamectin (optionally        STRONGHOLD™), a milbemycin (optionally milbemectin, milbemycin        oxime, moxidectin or nemadectin), doramectin (optionally        DECTOMAX™), eprinomectin or abamectin; or a thiazolide class        drug (optionally, nitazoxanide or tizoxanide) and oseltamivir        (or TAMIFLU™),    -   and optionally the thiazolide class drug (optionally,        nitazoxanide or tizoxanide) is formulated or administered with        ribavirin or tribavirin (or COPEGUS™, REBETOL™, or VIRAZOLE™),        and an avermectin class drug such as ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin;    -   (p) plitidepsin (also known as dehydrodidemnin B), or APLIDIN™        (PharmaMar, S. A.);    -   (q) an inhibitor or S-phase kinase-associated protein 2 (SKP2),        or dioscin, or niclosamide, or NICLOCIDE™, FENASAL™, or        PHENASAL™    -   (r) ritonavir (or NORVIR™), ribavirin or tribavirin (or COPEGUS™        REBETOL™, or VIRAZOLE™), interferon beta 1 b, or a combination        of ribavirin and interferon beta, or a combination of lopinavir        and ritonavir (or NORVIR™) and interferon-beta-1b;    -   (s) a nucleoside analog reverse-transcriptase inhibitor (NRTI)        (optionally abacavir, or ZIAGEN™), acyclovir or aciclovir        (optionally ZOVIRAX™), adefovir (optionally HEPSERA™),        amantadine(optionally GOCOVRI™, SYMADINE™, SYMMETREL™),        rintatolimod (or AMPLIGEN™), amprenavir (optionally,        AGENERASE™), aprepitant (or EMEND™), umifenovir (or ARBIDOL™)        atazanavir (or REYATAZ™), atazanavir (or REYATAZ™), tenofovir, a        combination of efavirenz and emtricitabine and tenofovir (or        ATRIPLA™), balavir, baloxavir marboxil (XOFLUZA™), bepotastine,        bevirimat, bictegravir, a combination of bictegravir and        emtricitabine and tenofovir alafenamide (or BIKTARVY™),        brilacidin, bivalirudin (or BIVALITROBAN™), cidofovir,        caspofungin, lamivudine and zidovudine (optionally, COMBVIR™),        cobicstat, colisitin, cocaine, darunavir, delavirdine, descovy,        didanosine, docosanol, dolutegravir, ecoliever, edoxudine,        efavirenz (optionally, SUSTIVA™), elvitegravir, emtricitabine,        enfuvirtide, foscarnet, fosfonet, galidesivir, ibacitabine,        icatibant, idoxuridine, ifenprodil, imiquimod, imunovir,        indinavir, inosine, an interferon (optionally interferon type I,        interferon type II and/or interferon type III), lamivudine (or        EPIVIR™, ZEFFIX™) lopinavir, loviride, ledipasvir, leronlimab,        maraviroc, methisazone, moroxydine, nelfinavir, nevirapine,        nexavir, nitazoxanide (optionally ALINIA™, NIZONIDE™), norvir, a        nucleoside analogue or derivative (optionally brincidofovir (or        TEMBEXA™), didanosine (or VIDEX™), favipiravir (also known as        T-705 or AVIGAN™, or favilavir, Toyama Chemical, Fujifilm,        Japan, or FABIFLU™ Glenmark Pharmaceuticals), vidarabine,        galidesivir (optionally, BCX4430, IMMUCILLIN-A™), remdesivir        (optionally, GS-5734™, Gilead Sciences), cytarabine,        gemcitabine, emtricitabine, lamivudine, zalcitabine, entecavir,        stavudine, telbivudine, zidovudine, idoxuridine and/or        trifluridine or any combination thereof), oseltamivir (or        TAMIFLU™), peginterferon alfa-2a, penciclovir, peramivir        (optionally, RAPIVAB™), perfenazine, pleconaril, plurifloxacin,        podophyllotoxin, pyramidine, raltegravir, rifampicin, ribavirin        or tribavirin (or COPEGUS™, REBETOL™, or VIRAZOLE™),        rilpivirine, rimantadine, ritonavir (or NORVIR™) saquinavir,        sofosbuvir, stavudine, telaprevir, tegobuv, tenofovir        alafenamide, tenofovir disoproxil, tenofovir, tipranavir,        trifluridine, trizivir, tromantadinc, truvada, valaciclovir        (optionally, VALTREX™), valganciclovir, valrubicin, vapreotide,        vicriviroc, vidarabine, viramidine, velpatasvir, vivecon,        zalcitabine, zanamivir (optionally, RELENZA™), zidovudine, an        immunosuppressive drug (optionally tocilizumab or atlizumab, or        ACTEMRA™, or ROACTEMRA™) or any combination thereof;    -   (t) an mucolytic therapy or drug, optionally acetylcysteine,        ambroxol, bromhexine (or BISOLVON™), carbocisteine, erdosteine,        mecysteine or dornase alfa, or an expectorant, optionally        guaifenesin;    -   (u) a viral, or a coronavirus or a COVID-19, protease inhibitor,        optionally ASC09 (CAS registry no. 1000287-05-7) (Janssen        Research and Development, LLC), ritonavir (or NORVIR™) or ASC09        and ritonavir (or NORVIR™), or a JAK1/2 inhibitor (optionally        baricitinib), optionally compound 11r (University of Lubeck,        Germany, see optionally, Zhang et al J. Med Chem 2020, Feb. 11,        2020), or darunavir, cobicistat or darunavir and cobicistat;    -   (v) an angiotensin-converting enzyme 2 (ACE2) inhibitor,        optionally to block the site of viral spike protein interaction        for anti-SARS-CoV-2 infection control;    -   (w) an anti-vascular endothelial growth factor (VEGF)        (optionally VEGF-A) drug or antibody, optionally bevacizumab;    -   (x) a protease inhibitor, optionally danoprevir, optionally a        serine protease inhibitor, optionally camostat or narlaprevir        (optionally ARLANSA™);    -   (y) anti-PD-1 checkpoint inhibitor, optionally camrelizumab;    -   (z) a compound or antibody capable of binding complement factor        C5 and blocking membrane attack complex formation, optionally        eculizumab;    -   (aa) a cathepsin inhibitor, optionally a cathepsin K, B or L        inhibitor, optionally relacatib;    -   (bb) thalidomide, or thalidomide and glucocorticoid (optionally        ciclesonide (or ALVESCO™, OMNARIS™, OMNIAIR™, ZETONNA™ or        ALVESCO™)) (optionally low-dose glucocorticoid), or and        thalidomide and celecoxib;

(cc) an antibacterial antibiotic or a macrolide drug,

-   -   wherein optionally the macrolide drug comprises azithromycin,        optionally dosaged at between about 50 mg to about 2000 mg per        dose or per day (optionally, ZITHROMAX™, or AZITHROCIN™,        optionally an oral extended- or delayed-release formulation of        azithromycin, or ZMAX™), clarithromycin (optionally, BIAXIN™),        erythromycin (optionally, ERYTHROCIN™), or fidaxomicin        (optionally, DIFICID™ or DIFICLIR™), troleandomycin (optionally,        TEKMISIN™), tylosin (optionally, TYLOCINE™ or TYLAN™),        solithromycin (optionally, SOLITHERA™), oleandomycin (or        SIGMAMYCINE™), midecamycin, roxithromycin, kitasamycin or        turimycin, josamycin, carbomycin or magnamycin, and/or        spiramycin,    -   and optionally the antibacterial antibiotic comprises a        tetracycline class drug, a glycylcycline or a fluorocycline        class drug, or an analogue thereof, and optionally the        tetracycline, glycylcycline or fluorocycline drug or analogue        thereof comprises or is: tetracycline or SUMYCIN™;        chlortetracycline or AUREOMYCIN™; oxytetracycline;        demeclocycline or DECLOMYCIN™, DECLOSTATIN™, LEDERMYCIN™,        BIOTERCICLIN™, DEGANOL™, DETECLO™, DETRAVIS™, MECICLIN™,        MEXOCINE™, CLORTETRIN™; lymecycline; meclocycline; metacycline;        minocycline or MINOCIN™; rolitetracycline; doxycycline, or        DORYX™, DOXYHEXA™, DOXYLIN™; tigecycline or TYGACIL™;        eravacycline or XERAVA™; sarecycline or SEYSARA™; omadacycline        or NUZYRA™; or any combination thereof,    -   and optionally the antibacterial antibiotic or macrolide drug,        optionally azithromycin (or ZMAX™), is administered in        combination with, and/or is combined with, chloroquine (or        ARALEN™), amodiaquine (or AMDAQUINE™, AMOBIN™), chloroquine        phosphate, chloroquine diphosphate and/or hydroxychloroquine        (optionally, PLAQUENIL™), and the combination is administered        commencing on the first, second, third, fourth, fifth, sixth,        seventh, eighth, ninth and/or tenth day of therapy, or is        administered for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or up to 20 or        more days, or for between about 1 to 21 days or longer, or is        administered until within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or up to        20 or more days of ending the therapy for treating, preventing,        ameliorating, slowing the progress of, decreasing the severity        of or preventing the coronavirus infection,    -   and optionally the chloroquine (or ARALEN™), chloroquine        phosphate, amodiaquine (or AMDAQUINE™, AMOBIN™), chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        is administered the entire length of the treatment but the        azithromycin, optionally dosaged at between about 50 mg to about        2000 mg per dose or per day (optionally, ZITHROMAX™, or        AZITHROCIN™, optionally an oral extended-release formulation of        azithromycin, or ZMAX™) administration is halted or ceased after        two, three, four, five or six days after treatment is commenced,        and optionally the azithromycin administration is replaced by a        tetracycline class drug, and optionally the tetracycline class        drug comprises doxycycline, or DORYX™, DOXYHEXA™, DOXYLIN™        administration,    -   and optionally the antibacterial antibiotic, optionally        azithromycin (optionally, ZITHROMAX™, or AZITHROCIN™, optionally        dosaged at between about 50 mg to about 2000 mg per dose or per        day,    -   and optionally an oral extended-release formulation of        azithromycin, or ZMAX™), is administered or formulated with an        avermectin class drug such as ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin, and/or cholecalciferol (vitamin D3) or calcifediol,    -   and optionally the antibacterial antibiotic comprises an        antimycobacterial drug, and optionally the antimycobacterial        drug comprises clofazimine (optionally LAMPRENE™);    -   (dd) an avermectin class drug such as ivermectin (optionally        STROMECTOL™, SOOLANTRA™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin, optionally dosaged and/or administered at about 5        microgram/kg to about 1 gram (g) per day, optionally formulated        or administered at about 1 to 10, 12, 15, 20, 30, 40, 50, 60,        70, 80, 100, 120, 140, 160, 180, 200, 220 or 240 mg per day, or        between about 1 to 240 mg per day, or between about 3 to 240 mg        per day,    -   optionally formulated or administered with an antibiotic        (optionally azithromycin, minocycline, amoxicillin, niclosamide,        nitazoxanide, hydroxychloroquine or doxycycline, and optionally        the doxycycline is at between about 25 to 600 mg per dose or per        day, or at about 100 mg per dose or per day, and optionally the        azithromycin is at between about 50 mg to 2000 mg per dose or        per day), optionally as a single or a divided dose, and        optionally formulated and administered as an inhalant or a mist        (optionally using a nebulizer, nasal spray or equivalent),        optionally formulated as an aerosol, spray, mist, liquid or        powder, optionally formulated as an aerosol, spray, mist, liquid        or powder,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is formulated with and/or administered with        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        with or without zinc (optionally a zinc sulphate, acetate,        gluconate or picolinate or any zinc salt), and optionally this        combination is administered weekly, or every two week, or one        every 5 to 28 days, as a prophylactic,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is administered alone in the morning (AM), and an        antibiotic (optionally doxycycline) and/or a chloroquine        (optionally, ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        is administered in the afternoon and/or evening,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is administered alone for 1, 2, 3, 4, 5, 6, 7, 8,        9, 10 or up to 20 or more days, followed by administration of an        antibiotic (optionally doxycycline) for a corresponding period        of days, and optionally repeating the cycle of dosaging,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is formulated or administered with:        -   (i) at least one antibiotic (wherein optionally the            antibiotic is doxycycline(optionally, DORYX™, DOXYHEXA™,            DOXYLIN™) (optionally formulated or administered at a dosage            of between about 25 mg to 600 mg per dose or per day), or            azithromycin (optionally, ZITHROMAX™, or AZITHROCIN™,            optionally dosaged at between about 50 mg to about 2000 mg            per dose or per day, optionally an oral extended-release            formulation of azithromycin, or ZMAX™) (optionally            formulated or administered at a dosage of between an about            50 mg to 2000 mg);        -   (ii) chloroquine (or ARALEN™), chloroquine phosphate,            chloroquine diphosphate and/or hydroxychloroquine            (optionally, PLAQUENIL™) (optionally formulated or            administered at a dosage of between an about 10 mg to 2000            mg per day);        -   (iii) a zinc (optionally a zinc sulphate, acetate, gluconate            or picolinate or any zinc salt) optionally formulated or            administered at a dosage of between about 1 mg to 250 mg;            and/or        -   (iv) at least one vitamin, and optionally the at least one            vitamin comprises: vitamin C optionally formulated or            administered at a dosage of between about 500 to 5000            units (U) per dose, and/or Vitamin D (or cholecalciferol)            optionally formulated or administered at a dosage of between            about 3,000 to 100,000 units per day, or between about            10,000 to 50,000 units a day,        -   and optionally the avermectin class drug such as ivermectin            (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,            EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a            milbemycin (optionally milbemectin, milbemycin oxime,            moxidectin or nemadectin), doramectin (optionally            DECTOMAX™), eprinomectin or abamectin is administered or            formulated alone or in combination with any of the above (i)            to (iv) (for example, at least one antibiotic, chloroquine            (or ARALEN™) chloroquine phosphate, chloroquine diphosphate            and/or hydroxychloroquine (optionally, PLAQUENIL™), zinc or            any zinc salt and/or at least one vitamin are formulated            (and administered) as oral formulations (for example, as            tablets, capsules, gels or geltabs), injectable            formulations, powders (for example, for inhalation or for            addition to an ingestible liquid) or liquids (for example,            for ingestion, infusion or injection);    -   (ee) chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) alone or with (or formulated with) or in combination        with any of (a) to (bb), or chloroquine, chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) and oseltamivir (or TAMIFLU™);    -   (ff) chloroquine (optionally, ARALEN™), chloroquine phosphate,        alone or with:        -   (i) an avermectin class drug such as ivermectin (optionally            STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,            QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin            (optionally milbemectin, milbemycin oxime, moxidectin or            nemadectin), doramectin (optionally DECTOMAX™), eprinomectin            or abamectin, optionally at a dosage of between about 3 to            340 mg per day, or about 6 mg to 60 mg, or about 10 mg to 80            mg dosages, or about 12 to 50 mg dosages;        -   (ii) vitamin D, vitamin D2 (or ergocalciferol), vitamin D3            (or cholecalciferol) optionally at a dosage of between about            3,000 to 100,000 units per day, or between about 10,000 to            50,000 units a day, and/or        -   (iii) with (i) and (ii) and zinc (optionally a zinc            sulphate, acetate, gluconate or picolinate or any zinc salt)            optionally at a dosage of between about 1 mg to 250 mg,            or (iv) the combination of (iii) also with a tetracycline            class drug, wherein optionally the tetracycline class drug            comprises doxycycline, or DORYX™, DOXYHEXA™, DOXYLIN™,            optionally dosages at between about 25 mg to 600 mg per day            or per dose, optionally between about 100 mg to 500 mg, or a            between about 200 mg to 400 mg per dose or per day;    -   (gg) colchicine, or COLCRYS™, MITIGARE™, optionally administered        or dosaged at between about 0.5 mg to 20 mg, or about 1 mg to 15        mg, or about 3 mg to 10 mg, or about 4 mg to 6 mg, per day for a        period of between about 7 and 21 days, or about 14 days, and        optionally also administered or formulated with an antibiotic        (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily);    -   (hh) a corticosteroid or glucocorticoid class drug such as        ciclesonide (or ALVESCO™, OMNARIS™, OMNIAIR™, ZETONNA™ or        ALVESCO™), budesonide (optionally RHINOCORT™ or PULMICORT™),        prednisolone (or ORAPRED™), methyl-prednisolone, prednisone (or        DELTASONE™ or ORASONE™) or hydrocortisone (or CORTEF™), wherein        optionally the corticosteroid or glucocorticoid class drug        (optionally ciclesonide) is inhaled,    -   or a selective estrogen receptor modulator (SERM), or toremifene        (or FARESTON™), or clomifene or clomiphene (or CLOMID™,        SEROPHENE™) wherein optionally the SERM is inhaled;    -   and optionally the corticosteroid class drug (for example        budesonide) is administered by inhalation, for example, in a        nebulized form, for example, between about 1 mg to 12 mg per day        of budesonide is administered by inhalation, or between about 6        to 80 mg per day of prednisolone is administered orally, or        between about 6 to 100 mg per day of prednisone is administered        orally, or between about 30 to 400 mg per day of hydrocortisone        is administered orally,    -   and optionally the corticosteroid class drug is formulated as a        powder or for administration in an inhaler or by nasal spray, or        for rectal administration,    -   and optionally the corticosteroid class drug (for example,        budesonide) is administered together with or in combination with        10 mg to 80 mg, an antibiotic (optionally azithromycin or a        tetracycline class drug,    -   wherein optionally the tetracycline class drug comprises        doxycycline, or DORYX™, DOXYHEXA™, DOXYLIN™), zinc or any zinc        salt and/or a vitamin (optionally vitamin D or calcifediol, D2        (or ergocalciferol), D3 (or cholecalciferol), C, E, B12, B6);    -   (ii) an anti-androgen drug, and optionally the anti-androgen        drug is bicalutamide, optionally CASODEX™, or dutasteride (or        AVODART™),        -   and optionally the anti-androgen drug is a nonsteroidal            anti-androgen (NSAA) or an androgen receptor (AR)            antagonist, and optionally the NSAA or AR antagonist            comprises proxalutamide (or its developmental name GT-0918)            (Suzhou Kintor Pharmaceuticals, Inc., a subsidiary of Kintor            Pharmaceutical Limited), or flutamide (or niftolide, or            EULEXIN™), or bicalutamide (or CASODEX™) or enzalutamide (or            XTANDI™),        -   and optionally the anti-androgen drug comprises a            5α-reductase inhibitor, and optionally the 5α-reductase            inhibitor comprises finasteride (or PROSCAR™, PROPECIA™, or            FINIDE™)        -   and optionally the anti-androgen drug, or NSAA, or            proxalutamide or bicalutamide, is administered together with            or in combination with an avermectin class drug such as            ivermectin (optionally STROMECTOL™), moxidectin (optionally            CYDECTIN™, EQUEST™, QUEST™), selamectin (optionally            STRONGHOLD™), a milbemycin (optionally milbemectin,            milbemycin oxime, eprinomectin or abamectin;        -   and optionally the anti-androgen drug, or NSAA, or            bicalutamide, proxalutamide, flutamide or niftolide,            bicalutamide, enzalutamide or dutasteride, is administered            at dosages of about 50 to 100 mg optionally administered            once, twice (BID), three times (TID) or four times a day, or            is administered at dosages of about 50 to 100 mg per day,        -   and optionally the anti-androgen drug, or NSAA, or            bicalutamide, proxalutamide, flutamide or niftolide,            bicalutamide, enzalutamide or dutasteride, is administered            with an avermectin class drug, or ivermectin, optionally            also administered with hydroxychloroquine, zinc and/or a            vitamin (optionally vitamin D (optionally vitamin D2, or            ergocalciferol, or Vitamin D3 or cholecalciferol, optionally            administered at about 1000 to 4000 ugm/day) or vitamin C, B            or A;    -   and optionally bicalutamide is administered together with or in        combination with an avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin,    -   and optionally bicalutamide is administered together with or in        combination with an avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin;    -   (jj) a hydrocortisone or cortisol (optionally CORTEF™,        SOLUCORTEF™), optionally hydrocortisone sodium succinate or        hydrocortisone acetate or dexamethasome (optionally DEXTENZA™,        OZURDEX™, NEOFORDEX™);    -   (kk) an alpha-ketoamide (α-ketoamide), wherein optionally the        alpha-ketoamide is a structure as described by Zhang et al, J.        Med. Chem. 2020, 63, 9, 4562-4578, or Meng et al Chem.        Sci. (2019) vol. 10, pg 5156 (optionally the structure KAM-2),    -   and optionally the alpha-ketoamide is formulated or administered        as an inhalant or a powder or mist, and optionally formulated or        administered with (optionally as an inhalant): an avermectin        class drug such as ivermectin (optionally STROMECTOL™),        moxidectin (optionally CYDECTIN™, EQUEST™, QUEST™), selamectin        (optionally STRONGHOLD™), a milbemycin (optionally milbemectin,        milbemycin oxime, moxidectin or nemadectin), doramectin        (optionally DECTOMAX™), eprinomectin or abamectin; an antibiotic        (optionally azithromycin or a tetracycline class drug, wherein        optionally the tetracycline class drug comprises doxycycline, or        DORYX™, DOXYHEXA™, DOXYLIN™); chloroquine (or ARALEN™),        chloroquine phosphate, chloroquine diphosphate and/or        hydroxychloroquine (optionally, PLAQUENIL™); zinc or any zinc        salt; remdesivir (optionally, GS-5734™, Gilead Sciences);        oseltamivir (or TAMIFLU™); and/or, hydrocortisone; or, any        combination thereof;    -   (ll) a compound, drug or formulation that decreases stomach acid        production or decreases stomach pH, wherein optionally the        compound, drug or formulation comprises famotidine, or PEPCID™,        and optionally the famotidine is administered at a dosage of        between about 10 to 60 mg per day, or between about 20 to 40 mg        per day, and optionally the famotidine is administered is        administered with: an avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin, and/or a tetracycline tetracycline class drug, and        optionally the tetracycline class drug comprises doxycycline, or        DORYX™, DOXYHEXA™, DOXYLIN™;    -   (mm) a dendrimer, optionally astodrimer sodium (Starpharma,        Melbourne, Australia);    -   (nn) an antihistamine class drug such as azelastine, or        ASTELIN™, OPTIVAR™, ALLERGODIL™, brompheniramine, fexofenadine        or ALLEGRA™ pheniramine or AVIL™, or chlorpheniramine;    -   (oo) a selective serotonin reuptake inhibitor (SSRI) class drug,        optionally fluvoxamine, or LUVOX™, FAVERIN™, FLUVOXIN™;    -   (pp) a nicotinic antagonist, a dopamine agonist or a        noncompetitive N-Methyl-d-aspartic acid or N-Methyl-d-aspartate        (NMDA) antagonist, wherein optionally the nicotinic antagonist,        dopamine agonist or noncompetitive NMDA antagonist is        1-adamantylamine or amantadine, or GOCOVRI™, SYMADINE™,        SYMMETREL™, optionally administered or dosaged at between about        50 mg to 150 mg, or about 100 mg, per day for a period of        between about 7 and 21 days, or about 14 days, and optionally        the nicotinic antagonist, dopamine agonist or noncompetitive        NMDA antagonist is also administered or formulated with an        antibiotic (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily),        and optionally the amantadine is formulated or administered at        100 mg per day for the first two days of treatment, which        optionally can then be elevated to 100 mg twice daily,        optionally for the next 10 days;    -   (qq) an immunosuppressive drug, wherein optionally the        immunosuppressive drug comprises tocilizumab or atlizumab, or        ACTEMRA™, or ROACTEMRA™, or a calcineurin inhibitor (CNI),        wherein the CNI comprises ciclosporin (or cyclosporine or        cyclosporin), or NEORAL™, or SANDIMMUNE™, or tacrolimus, or        PROTOPIC™, or PROGRAF™, and optionally the immunosuppressive        drug is also administered or formulated with an antibiotic        (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily),    -   and optionally the calcineurin inhibitor (CNI), wherein the CNI        comprises ciclosporin (or cyclosporine or cyclosporin) is        formulated combination of CNI (optionally cyclosporine) at a        dose of 3 mg/kg (180 mg daily) together with 12 mg ivermectin        once, and optionally also plus zinc 50 mg base and doxycycline        100 mg bid, optionally all for 10 days;    -   (rr) a protein kinase inhibitor, wherein optionally the protein        kinase inhibitor is a p38 mitogen-activated protein kinase        inhibitor, or ralimetinib, and optionally the protein kinase        inhibitor is also administered or formulated with an antibiotic        (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily);    -   (ss) an anti-inflammatory therapy or at least one        anti-inflammatory therapy drug, wherein optionally the        anti-inflammatory therapy or drug comprises: a sphingosine        kinase-2 (SK2) selective inhibitor (optionally, opaganib        (optionally, YELIVA™), sirolimus, a JAK1/2/TYK2 inhibitor        (optionally ruxolitinib), an anti-CD47 mAb (optionally        meplazumab), a cyclooxygenase (COX) (optionally, COX2)        inhibitor, a glucocorticoid (optionally a synthetic        glucocorticoid, hydrocortisone, dexamethasone (or DEXTENZA™,        OZURDEX™, or NEOFORDEX™) or cortisol, or CORTEF™), plitidepsin        or dehydrodidemnin B, or APLIDIN™, or a nonsteroidal        anti-inflammatory drug (NSAID), wherein optionally the NSAID        comprises indomethacin (or indomethacin) or INDOCID™ or        INDOCIN™, or naproxen, or NAPROSYN™ or ALEVE™, or a        cyclooxygenase inhibitor, or a COX-1 or an COX-2 inhibitor, or        aspirin, or ibuprofen or ADVIL™, MOTRIN™ or NUROFEN™, or        celecoxib or CELEBREX™, or parecoxib or DYNASTAT™, or etoricoxib        or ARCOXIA™,    -   and optionally the anti-inflammatory therapy or        anti-inflammatory therapy drug is also administered or        formulated with an antibiotic (optionally azithromycin or        doxycycline), ivermectin, hydroxychloroquine (optionally,        PLAQUENIL™) and/or zinc or any zinc salt (optionally zinc        sulfate, optionally at (50 mg daily),    -   and optionally opaganib, or YELIVA™, or opaganib, or YELIVA™        administered or formulated together with an oral and/or inhaled        or aerosol chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™),    -   and optionally the opaganib or YELIVA™ is formulated or        administered at a dosage of QD (once a day), bid (twice a day)        or tid (three times a day) at a dosage of between about 100 to        600 mg per day or per dosage, or at about 100, 200, 300, 400,        500 or 600 mg per day or per dosage,    -   and optionally the opaganib, or YELIVA™ is also administered or        formulated with an antibiotic (optionally azithromycin or        doxycycline), ivermectin (optionally at 12 mg ivermectin,        optionally administered on days 1, 3, 6 and 8),        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily);    -   (tt) a calcium channel blocker, or verapamil (or ISOPTIN™,        CALAN™), or a voltage gated potassium (KCNH2) channel or a        voltage gated calcium channel (CACNA2D2) blocker, or amiodarone        (or CORDARONE™, NEXTERONE™);    -   (uu) suramin, or ANTRYPOL™, BAYER 305™, or GERMANIN™;    -   (vv) a peroxisome proliferator-activated receptor (PPAR)        agonist, wherein optionally the PPAR agonist comprises        fenofibrate, or TRICOR™, FENOBRAT™, FENOGLIDE™, or LIPOFEN™, or        a combination of fenofibrate and simvastatin, or CHOLIB™,        optionally the PPAR agonist comprises a combination of        fenofibrate and pravastatin, or PRAVAFENIX™, or the PPAR agonist        comprises bezafibrate, or BEZALIP™, or combination of        bezafibrate and chenodeoxycholic acid, or HEPACONDA™, or        aluminium clofibrate, or alfibrate, or ciprofibrate, or        clinofibrate or LIPOCLIN™, or clofibrate or ATROMID-S™, or        clofibride, or gemfibrozil or LOPID™, or ronifibrate, or        simfibrate or CHOLESOLVIN™, or any combination thereof,    -   (ww) a synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or a prodrug of N4-hydroxycytidine,        optionally molnuvpiravir (Merck), or favipiravir (also known as        T-705 or AVIGAN™, or favilavir, Toyama Chemical, Fujifilm,        Japan, or FABIFLU™, Glenmark Pharmaceuticals),    -   wherein the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is given as between        about 10 mg to 3 gm per dose, or between about 10 mg to 3 gm per        day, or can be dosed either as a single dose or given one, two,        three or four times a day, or is administered at 200 to 800 mg        twice daily, or 200, 400, 600 or 800 mg twice daily, or at 200        to 800 mg three times a day, or at 200, 400, 600 or 800 mg three        times a day, or is administered at 200 to 800 mg three times a        day for between about 2 to 15 days, or for about 2, 3, 4, 5, 6,        7, 8, 9, 10, 11 or 12 days, and optionally when combined with        other drugs a lower dosage is used, optionally administered at        100 or 200 mg three times a day for between about 5 to 15 days,        or for about 7, 8, 9, 10, 11 or 12 days,    -   and optionally the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is administered with an        avermectin class drug (optionally ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin),    -   and optionally the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is administered with an        avermectin class drug (optionally ivermectin) with an        antibiotic, and optionally the antibiotic comprises        azithromycin, minocycline, amoxicillin, niclosamide,        nitazoxanide, hydroxychloroquine or doxycycline), and optionally        the synthetic nucleoside analog or derivative, avermectin class        drug, and antibiotic are administered together or as separate        formulations, and optionally are administered every one, two,        three, four or five weeks for between about one month and one        year or more;    -   and optionally molnuvpiravir, ivermectin and hydroxychloroquine        are administered together or as separate formulations, and        optionally are administered every one, two, three, four or five        weeks for between about one month and one year or more;    -   and optionally the synthetic nucleoside analog or derivative        (optionally N4-hydroxycytidine, or the prodrug of        N4-hydroxycytidine, optionally molnuvpiravir or favipiravir),        and antibiotic (optionally doxycycline or hydroxychloroquine) is        administered with zinc (optionally a zinc sulphate, acetate,        gluconate or picolinate, or zinc oxide nanoparticles, optionally        at a dosage of between about 1 mg to 250 mg, or about 50 mg per        day) and/or a vitamin, optionally vitamin C or D),    -   and optionally the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is administered with an        antibiotic (optionally the antibiotic comprises azithromycin,        minocycline, amoxicillin, niclosamide, nitazoxanide,        hydroxychloroquine or doxycycline), optionally also administered        with zinc (optionally a zinc sulphate, acetate, gluconate or        picolinate, or zinc oxide nanoparticles, optionally at a dosage        of between about 1 mg to 250 mg, or about 50 mg per day) and/or        a vitamin, optionally vitamin C or D,    -   and optionally the anti-androgen drug, or NSAA, or bicalutamide,        proxalutamide, flutamide or niftolide, bicalutamide,        enzalutamide or dutasteride, is administered with colchicine (or        COLCRYS™, MITIGARE™), and optionally also zinc and/or a vitamin        (optionally vitamin D (optionally vitamin D2, or ergocalciferol,        or Vitamin D3 or cholecalciferol, optionally administered at        about 1000 to 4000 ugm/day), or vitamin C, B or A),    -   and optionally the anti-androgen drug, or NSAA, or bicalutamide,        proxalutamide, flutamide or niftolide, bicalutamide,        enzalutamide or dutasteride, is administered with an antibiotic        (optionally azithromycin or doxycycline), and optionally also        zinc and/or a vitamin (optionally vitamin D (optionally vitamin        D2, or ergocalciferol, or Vitamin D3 or cholecalciferol,        optionally administered at about 1000 to 4000 ugm/day), or        vitamin C, B or A), and optionally also with hydroxychloroquine;    -   (xx) an anti-malarial drug, wherein optionally the anti-malarial        drug comprises mefloquine (or LARIAM™, MEPHAQUIN™, or MEFLIAM™);    -   (yy) an antisera or an antibody or antibody or vaccine therapy        for treating, preventing or ameliorating a microbial or a viral        infection (optionally a coronavirus infection, optionally a        COVID-19 infection) or a microbial infection (optionally a        protozoan, helminthiasis, insect and/or parasitic infection),        and optionally the antibody comprises a monoclonal antibody, and        optionally the monoclonal antibody comprises sotrovimab        (GlaxoSmithKline and Vir Biotechnology), or casirivimab,        imdevimab or casirivimab and imdevimab (REGEN-COV™) (Regeneron),        or bamlanivimab oretesevimab or bamlanivimab and etesevimab        (Junshi Biosciences), or tocilizumab or ACTEMRA™ or ROACTEMRA™        (Hoffmann-La Roche), and optionally the vaccine comprises        tozinamera or COMIRNATY™ (Pfizer), or elasomeran or SPIKEVAX™        (Moderna), or SPUTNIK V™ or Gam-COVID-Vac (Gamaleya Research        Institute), or AZD1222 or COVISHIELD™ or VAXZEVRIA™        (Oxford-AstraZeneca),    -   and optionally the antibody or antibody therapy comprises or is        contained in a convalescent sera or plasma, and/or    -   (zz) any combination of (a) to (yy), and optionally any of these        combinations is administered very 2, 3, 4, 5, 6, 7, 8, 9 or 10        or more days for between about 1 month and one year or more,    -   and optionally any one or several or all of (a) to (zz) with an        (or formulated with or formulated as an) inhaled or aerosol        formulation such as a powder, spray or a mist or aerosol, and/or        formulated with or formulated as an oral, intramuscular (IM) or        intravenous (IV) formulation, wherein optionally both the        inhaled (or aerosol) and the oral, IV and/or IM formulations are        administered simultaneously or sequentially,    -   and optionally the inhaled or aerosol formulation comprises        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        and/or oral chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) administered simultaneously or overlapping,    -   and optionally the inhaled or aerosol formulation comprises an        avermectin class drug such as ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin,    -   and optionally any one or several or all of (a) to (zz), or any        therapeutic combination of drugs or a drug, or a pharmaceutical        dosage form as provided herein, are administered orally,        intramuscularly, subcutaneously, topically, by use of an enema,        intravaginally, or intravenously, or administration is by        subcutaneous administration, sublingual administration,        inhalation or by aerosol (optionally by inhalation of a liquid,        an aerosol, a spray, a mist or a powder), by absorbable patch,        by use of an implant, or by use of an enema or a suppository.

In alternative embodiments, the anti-viral drug or medication, oranti-microbial drug, is or comprises: molnupiravir, efavirenz(optionally, SUSTIVA™), tenofovir, emtricitabine and tenofovir,nevirapine (or the combination efavirenz with emtricitabine andtenofovir, or ATRIPLA™), amprenavir (optionally, AGENERASE™), nelfinavir(optionally, VIRACEPT™) and/or remdesivir (optionally, GS-5734™, GileadSciences), a viral RNA-dependent RNA polymerase inhibitor, optionallygalidesivir, a nucleoside analog reverse-transcriptase inhibitor (NRTI)(optionally abacavir, or ZIAGEN™),

-   -   and optionally the anti-viral drug or medication is or comprises        an anti-retroviral drug or drug combination, and optionally the        anti-retroviral drug or drug combination comprises: darunavir        and cobicistat (optionally, REZOLSTA™ or PREZCOBIX™); atazanavir        and cobicistat (or EVOTAZ™); abacavir, lamivudine and        dolutegravir (TRIUMEQ™); tenofovir (or disoproxil or        emtricitabine) and elvitegravir and cobicistat (optionally,        STRIBILD™); tenofovir (or disoproxil or emtricitabine) and        elvitegravir and cobicistat (COMPLERA™ or EVIPLERA™);        molnupiravir, efavirenz (optionally, SUSTIVA™), emtricitabine        and tenofovir (ATRIPLA); lamivudine, nevirapine and stavudine        (optionally, TRIOMUNE™); atazanavir and cobicistat (optionally,        EVOTAZ™); lamivudine and raltegravir (optionally, DUTREBIS™);        lamivudine and dolutegravir (or DOVATO™); doravirine, lamivudine        and tenofovir (optionally, DELSTRIGO™); or lamivudine,        zidovudine and nevirapine (optionally, CUOVIR-N™);    -   and optionally the additional anti-viral drug or medication, or        anti-microbial drug, is formulated with the chloroquine        (optionally, ARALEN™), chloroquine phosphate, chloroquine        diphosphate, hydroxychloroquine (optionally, PLAQUENIL™),        lopinavir, ritonavir (or NORVIR™) and/or oseltamivir or is        formulated separately from the chloroquine (optionally,        ARALEN™), chloroquine phosphate, chloroquine diphosphate,        hydroxychloroquine (optionally, PLAQUENIL™), lopinavir,        ritonavir (or NORVIR™) and/or oseltamivir,    -   and optionally the anti-viral drug or medication, or        anti-microbial drug, or palliative agent comprises or further        comprises: magnesium (Mg, optionally administer        intravenously (IV) to maintain a blood concentration of between        about 2.0 and 2.4 mmol/1); zinc or any zinc salt (optionally a        zinc sulphate, acetate, gluconate or picolinate, optionally        administered at about 75 to 100 mg/day or at a dosage of between        about 1 mg to 250 mg); at least one vitamin, wherein optionally        the at least one vitamin comprises vitamin K, vitamin D or        calcifediol (optionally D2 (or ergocalciferol) or Vitamin D3 or        cholecalciferol), optionally administered at about 1000 to 4000        ugm/day), vitamin B6 (or pyridoxine), vitamin B12, vitamin E,        and/or vitamin C (optionally administered at 500 mg bid); a        flavonoid, plant flavonol or quercetin optionally administered        at between about 250 to 500 mg bid; atorvastatin, or LIPITOR™,        SORTIS™ (optionally administered at between about 40 mg/day to        80 mg/day); or, melatonin, or CIRCADIN™, SLENYTO™ (optionally        between about 6 to 12 mg a day, optionally, at night), any of        which are optionally given enterally or parenterally.        Anti-Clotting or Blood Thinning Agents

In alternative embodiments for practicing methods as provided herein, toaddress the possibility of blood clotting, whether the blood clotting iscaused by the infectious agent, the administered inactivated orattenuated causative agent of the infection, or the live, viable orinfectious causative agent of the infection, and/or the vaccine or forany another reason, an anti-clotting or anti-coagulant or blood thinningdrug or agent is also administered, for example, before and/or at thecommencement of the vaccination, and optionally is continued for betweenabout 1 to 2 or 1 to 6 weeks after the vaccination, or for the durationof the anti-microbial drug treatment though administration of a secondor booster vaccination, and/or for between about 1 to 2 weeks afteradministration of the second or booster vaccination.

In alternative embodiments, the anti-clotting agent or anti-coagulant orblood thinning drug or agent comprises aspirin, for example betweenabout 100 mg to 500 mg aspirin administered (for example, in themorning, or AM, or MANE) for 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, 13 or 14or more days commencing on the day of the vaccination or commencing oneor two days before the vaccination day.

In alternative embodiments, antiplatelet drugs that can be used includeclopidogrel (PLAVIX™), prasugrel (EFFIENT™) and ticagrelor (BRILINTA™).

In alternative embodiments, the anti-clotting or anti-coagulant agent orblood thinning drug or agent comprises: heparin; warfarin (orCOUMADIN™); a coumarin; phenprocoumon (or MARCUMAR™); rivaroxaban(XARELTO™); dabigatran (PRADAXA™); apixaban (ELIQUIS™); edoxaban(LIXIANA™) and/or betrixaban (BEVYXXA™).

Vaccines

In alternative embodiments, provided are methods for treating,ameliorating, decreasing the chances of having any adverse effects from,decreasing the severity of adverse effects from, or preventing aninfection by administration of an antibiotic and/or an anti-viral drugsand a vaccine directed to a causative agent of the infection, and/or aninactivated or attenuated causative agent of the infection, or a live,viable or infectious causative agent of the infection.

In alternative embodiments, vaccines used to practice methods asprovided herein are directed to an exterior-expressed protein of apathogen, for example, where the pathogen is a bacteria or a virus, forexample, the exterior-expressed protein comprises a spike protein of avirus, for example, a spike protein of a coronavirus, for example, aCovid-19 spike protein.

In alternative embodiments, vaccines used to practice methods asprovided herein are formulated and administered using any formulations,protocols or techniques known in the art, for example, pharmaceuticalformulations or vaccines as provided herein can be administered aspeptides, or can be administered in the form of nucleic acids thatencode the immunogenic peptides or proteins. In alternative embodiments,vaccines used to practice methods as provided herein comprise orally andintra-nasally administered vaccines.

In alternative embodiments, vaccines used to practice methods asprovided herein comprise administration of inactivated pathogen, forexample, an inactivated virus (optionally an inactivated whole or entirepathogen (or virus) or substantially a whole or entire pathogen (orvirus), for example, an inactivated coronavirus, for example, andinactivated COVID-19 virus, for example, as manufactured by Valneva,France), Sinopharm, or Bharat Biotech. In alternative embodiments, thepathogen (or virus) is inactivated using a chemical, for example, abeta-propiolactone (BPL) or equivalent, or any means used to inactivatea viruses for a vaccine. This type of inactivation can preserve thestructure of the pathogen (for example, viral) proteins, as they wouldoccur in nature. This means the immune system will be presented withsomething similar to what occurs naturally and mount a strong immuneresponse. In alternative embodiments, after being inactivated, thevaccine (or, the inactivated pathogen, or virus) is highly purified. Inalternative embodiments, an adjuvant (or any immune stimulant) is addedor co-administered to induce a boosted or strong immune response.

In alternative embodiments, vaccines used to practice methods asprovided herein are DNA vaccine or RNA vaccines. For example, inalternative embodiments the immunogen-encoding nucleic acid can be a DNAencoding one or more immunogenic peptides or proteins, and the DNA canbe carried in an expression vehicle such as a viral vector, for examplean adenovirus vector such as an Ad5 or adeno-associated vector (AAV). Inalternative embodiments, recombinant adenoviruses as used in vaccines asprovided herein can be as described in U.S. patent application no. US20200399323 A1, which describes for example recombinant adenovirusesincluding a deletion in or of the E1 region or any deletion that rendersthe virus replication-defective, for example, the replication-defectivevirus can include a deletion in one or more of the E1, E3, and/or E4regions; or, can be as described in U.S. patent application no. US20190382793 A1, which described how to make recombinant adenoviruses forgene therapy.

In alternative embodiments, the immunogen-encoding nucleic acid can bean RNA, for example, mRNA, which can be formulated in a lipidformulation or a liposome and injected for example intramuscularly (IM),for example using formulations and methods as described in U.S. patentapplication no. US 20210046173 A1, which describes delivering to asubject (for example, via intramuscular administration) an immunogeniccomposition that comprises a RNA (for example, mRNA) that comprises anopen reading frame (ORF) that comprises (or consists of, or consistsessentially of) an immunogenic or antigenic sequence as provided herein;wherein optionally the RNA (or the DNA-carrying expression vehicle) isformulated in a liposome, or a lipid nanoparticle (LNP), ornanoliposome, that comprises: non-cationic lipids comprise a mixture ofcholesterol and DSPC, or a PEG-lipid, or PEG-modified lipid, or LNP, oran ionizable cationic lipid; or a mixture of(13Z,16Z)-N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine, cholesterol,DSPC, and PEG-2000 DMG. In alternative embodiments, the PEG-lipid is1,2-Dimyristoyl-sn-glycerol methoxypolyethylene glycol (PEG-DMG),PEG-disteryl glycerol (PEG-DSG), PEG-dipalmetoleyl, PEG-dioleyl,PEG-distearyl, PEG-diacylglycamide (PEG-DAG), PEG-dipalmitoylphosphatidylethanolamine (PEG-DPPE), orPEG-1,2-dimyristyloxlpropyl-3-amine (PEG-c-DMA), or, the PEG-lipid isPEG coupled to dimyristoylglycerol (PEG-DMG). In alternativeembodiments, the LNP comprises 20-99.8 mole % ionizable cationic lipids,0.1-65 mole % non-cationic lipids, and 0.1-20 mole % PEG-lipid. Inalternative embodiments, the LNP comprises an ionizable cationic lipidselected from the group consisting of(2S)-1-({6-[(3))-cholest-5-en-3-yloxy]hexyl}oxy)-N,N-dimethyl-3-[(9Z)-octadec-9-en-1-yloxy]propan-2-amine;(13Z,16Z)-N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine; andN,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]heptadecan-8-amine; or apharmaceutically acceptable salt thereof, or a stereoisomer of any ofthe foregoing. In alternative embodiments, the PEG modified lipidcomprises a PEG-modified phosphatidylethanolamine, a PEG-modifiedphosphatidic acid, a PEG-modified ceramide, a PEG-modified dialkylamine,a PEG-modified diacylglycerol, a PEG-modified dialkylglycerol, andmixtures thereof. In alternative embodiments, the ionizable cationiclipid comprises: 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane(DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate(DLin-MC3-DMA), di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319),(13Z,16Z)-N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine,(12Z,15Z)-N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine, andN,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]heptadecan-8-amine. In oneembodiment, the lipid is(13Z,16Z)-N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine orN,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]heptadecan-8-amine, each ofwhich are described in PCT/US2011/052328, the entire contents of whichare hereby incorporated by reference. In some embodiments, anon-cationic lipid of the disclosure comprises1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC),1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE),1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC),1,2-dimyristoyl-sn-gly cero-phosphocholine (DMPC),1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC),1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC),1,2-diundecanoyl-sn-glycero-phosphocholine (DUPC),1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC),1,2-di-O-octadecenyl-sn-glycero-3-phosphocholine (18:0 Diether PC),1-oleoyl-2 cholesterylhemisuccinoyl-sn-glycero-3-phosphocholine(OChemsPC), 1-hexadecyl-sn-glycero-3-phosphocholine (C16 Lyso PC),1,2-dilinolenoyl-sn-glycero-3-phosphocholine,1,2-diarachidonoyl-sn-glycero-3-phosphocholine,1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine,1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (ME 16.0 PE),1,2-distearoyl-sn-glycero-3-phosphoethanolamine,1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine,1,2-dilinolenoyl-sn-glycero-3-phosphoethanolamine,1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine,1,2-didocosahexaenoyl-sn-glycero-3-phosphoethanolamine,1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG),sphingomyelin, or mixtures thereof.

Attenuated, or Live, Viable or Infectious Causative Agent of theInfection

In alternative embodiments, provided are methods for treating,ameliorating, decreasing the chances of having any adverse effects from,decreasing the severity of adverse effects from, or preventing aninfection, comprising administering to a subject or an individual inneed thereof:

-   -   (a) at least one antibiotic and/or anti-viral drug capable of        killing a causative agent of the infection, or completely or        partially inhibiting the ability of the causative agent of the        infection to replicate or become infectious or cause pathology        in the subject or the individual in need thereof; and,    -   (b) (i) at least one dose of a vaccine directed to the causative        agent of the infection upon entry into the vaccinated subject or        individual in need thereof,    -   wherein the vaccine is capable of initiating an immune response        in the individual that can substantially or partially kill or        neutralize a causative agent of the infection, or the vaccine        can completely, substantially or partially inhibit the ability        of the causative agent of the infection to replicate, or be        infectious, or cause pathology, in the subject or the individual        in need thereof, and/or    -   (ii) an inactivated or attenuated causative agent of the        infection, or a live, viable or infectious causative agent of        the infection, wherein optionally the live causative agent of        the infection is a completely or partially attenuated version of        the causative agent,    -   wherein at least one dosage of the at least one antibiotic        and/or anti-viral drug is administered 1, 2, 3, 4, 5, 6, 7, 8,        9, 10, 11, 12, 13 or 14 or more days before, or on the day of, a        first dose of the at least one of a plurality of dosages of the        vaccine is administered, or a dose of the inactivated,        attenuated causative agent of the infection, or the live, viable        or infectious causative agent of the infection.

In alternative embodiments, the causative agent of the infection is orcomprises a bacteria, protozoan or a virus, or

-   -   the causative agent of the infection is or comprises the        causative agent of:        -   a viral infection, optionally a coronavirus, a virus that            causes a common cold, an influenza virus (optionally an            influenza A, B or C), a hepatitis virus, a respiratory            syncytial virus (RSV), a Paramyxoviridae or measles virus, a            Paramyxovirus or mumps virus, a Herpes simplex virus (HSV),            a Cytomegalovirus (CMV), a Rubivirus or rubella virus, an            Enterovirus, a viral meningitis, a rhinovirus, a human            immunodeficiency virus (HIV), a varicella-zoster or            chickenpox virus, an Orthopoxvirus or variola or smallpox            virus, an Epstein-Barr virus (EBV), an Adenovirus, a            Hantavirus, a Flaviviridae or Dengue virus, a Zika virus, or            a chikungunya virus infection,        -   a coronavirus infection, optionally a COVID-19 or a COVID-19            variant infection, or a Middle East respiratory syndrome            virus (MERS-CoV) infection;        -   malaria caused by a parasite of the genus Plasmodium            (optionally P. vivax, P. falciparum, P. malariae, P. ovale,            or P. knowlesi);        -   dengue fever or dengue shock syndrome caused by a virus of            the Flaviviridae family or a dengue virus;        -   a Flaviviridae family virus infection or a hepatitis or a            hepatocellular carcinoma associated with viral hepatitis            caused by a virus of the Flaviviridae family or a virus of            the genus Hepacivirus or Hepacivirus C virus or hepatitis C;        -   filariasis, leprosy or streptocerciasis or an infection            caused by a parasite of the superfamily Filarioidea            (optionally Brugia malayi, Brugia timori, Wuchereria            bancrofti, Loa loa, Mansonella streptocerca, Mansonella            ozzardi, or Mansonella perstans);        -   leprosy or an infection caused by a parasite of the genus            Mycobacterium (optionally M. leprae or M. lepromatosis);        -   river blindness or onchocerciasis caused by a parasitic worm            or a parasite of the genus Onchocerca (optionally O.            volvulus);        -   a hookworm or a roundworm infection caused by a parasite of            the genus Ancylostoma (optionally A. duodenale or A.            ceylanicum) or Necator (optionally N. americanus);        -   trichuriasis or a whipworm infection caused by a parasite of            the genus Trichuris (optionally T. trichiura); roundworm or            an Ascaris infection that is caused by Ascaris lumbricoides;        -   scabies or a mite-carried infection caused by the parasite            of the genus Sarcoptes (optionally S. scabiei);        -   typhus or an infection caused by a lice or a parasite of the            order Phthiraptera (optionally Pediculus humanus capitis);        -   enterobiasis or an infection caused by a pinworm or a            parasite of the genus Enterobius (optionally E.            vermicularis); and/or        -   pulicosis or an infection caused by a flea or an insect of            the order Siphonaptera or of the genus Pulex (optionally P.            irritans).

In alternative embodiments, the inactivated or attenuated causativeagent of the infection, or the live, viable or infectious causativeagent of the infection is administered orally or by inhalation.Alternatively, the inactivated or attenuated causative agent of theinfection, or the live, viable or infectious causative agent of theinfection can be administered by inclusion of the live, viable orinfectious causative agent of the infection in a liquid (optionally tobe administered as a drink or in drops such as nasal drops), a tablet, alozenge, an aerosol, spray, or mist formulation that is inhaled oradministered nasally or orally (optionally, by a puffer of a nebulizer),or the inactivated or attenuated causative agent of the infection, orthe live, viable or infectious causative agent of the infection isformulated in a liquid (optionally the liquid is a sterile saline)solution which is ingested or gargled by the individual in need thereof.

In alternative embodiments, the source of the inactivated or attenuatedcausative agent of the infection, or the administered live, viable orinfectious causative agent of the infection can be from an infectedindividual, such as a human patient, a domesticated, wild or lab animal,or from a lab-grown culture. In alternative embodiments, the source ofthe administered inactivated or attenuated causative agent of theinfection, or the live, viable or infectious causative agent of theinfection is from swab or sputum or other biological samples from aninfected individual or patient. In alternative embodiments, the sputumor other biological sample from an infected individual or patient isdiluted in a water or a saline prior to administrations.

In alternative embodiments, the administered inactivated or attenuatedcausative agent of the infection, or the live, viable or infectiouscausative agent of the infection is attenuated (in other words, itsability to cause pathogenesis is completely, substantially or partiallyabrogated or diminished, for example is genetically deleted ordiminished by genomic engineering).

In alternative embodiments, to generate an attenuated (e.g., completedinactivated) version of a causative agent of the infection to beadministered, the causative agent of the infection is passaged multipletimes in culture (or in vitro) or in an animal (or in vivo), wherevariants from each passage are selected for a phenotype and/or genotypethat has diminished ability to cause pathogenesis.

In alternative embodiments, to generate an attenuated (e.g., completedinactivated, completely non-infectious) version of a causative agent ofthe infection to be administered, the causative agent of the infectionis treated with radiation and/or a chemical. For example, the chemicalcan be iodine (for example, povidone-iodine or PVP-I, also known asiodopovidone, or BETADINE™, WOKADINE™, PYODINE™), or any complex ofpolyvinylpyrrolidone and iodine, alcohol and/or formalin.

In alternative embodiments, the causative agent of the infection isrendered inactive, or non-infectious, by exposing the causative agent ofthe infection to iodine or povidone-iodine or PVP-I (povidone is alsoknown as polyvinylpyrrolidone (PVP), or1-vinyl-2-pyrrolidinon-polymere), also known as iodopovidone, orBETADINE™, WOKADINE™, PYODINE™, as in the production of nasodine(Firebrick Pharma Pty Ltd, Australia). Povidone-iodine is a chemicalcomplex of povidone, hydrogen iodide, and elemental iodine or triiodide(I³⁻); and it contains 10% povidone, with total iodine species equaling10,000 ppm or 1% total titratable iodine, and it works by releasingiodine which results in the death of a range of microorganisms. Inalternative embodiment, the causative agent of infection is mixed withPVP-I and water, ethyl alcohol, isopropyl alcohol, polyethylene glycolor glycerol.

In alternative embodiments, the attenuated, or inactivated, causativeagent, or live causative agent, is administered with an adjuvant, wherethe adjuvant can comprise: an inorganic compound such as alum (e.g.,potassium alum), an aluminium salt or aluminium hydroxide, aluminiumphosphate, or calcium phosphate; an oil such as paraffin oil, propolisor Adjuvant 65; a bacterial product such as killed bacteria of the genusBordetella or Mycobacterium or of the species Bordetella pertussis orMycobacterium bovis; a plant saponin or soybean extract; a cytokine suchas interleukin-1 (IL-1), IL-2 or IL-12; Freund's complete adjuvant orFreund's incomplete adjuvant; and/or, an organic compound such assqualene.

In alternative embodiments, the attenuated, or inactivated, causativeagent, or live causative agent, with or without an adjuvant, isadministered by nasal spray or nebulizer, or orally for example bylozenge, tablet, capsule or geltab, or by subcutaneous injection, orintramuscularly (IM), or by suppository, or via an implant.

In alternative embodiments, attenuated viruses are made using a liveattenuated codon-pair-deoptimized virus approach as described forexample in Wang et al PNAS, Jul. 20, 2021, vol. 18 (29) e2102775118; oras described by Coleman et al. Science 320, 1784-1787 (2008), or Chenget al J. Virol. 89, 3523-3533 (2015), or Gonsalves-Carneiro, mBio 12,e02238-20 (2021).

For example, methods as provided herein comprise administration of theWang et al, COVI-VAC™ attenuated virus, which was developed by recodinga segment of the viral spike protein with synonymous suboptimal codonpairs (codon-pair deoptimization), thereby introducing 283 silent(point) mutations. As described by Wang et al, synthetic highlyattenuated live vaccine is generated by recoding portions of the WTSARS-CoV-2 genome according to the SAVE algorithm of codon-pair biasdeoptimization. In addition, the furin cleavage site within the spikeprotein was deleted from the viral genome for added safety of thevaccine strain. Except for the furin cleavage site deletion, theCOVI-VAC and parental SARS-CoV-2 amino acid sequences are identical,ensuring that all viral proteins can engage with the host immune systemof vaccine recipients. Attenuated viruses can be generated from viralgenomes recover from WT SARS-CoV-2, strain USA-WA1/2020 (GenBankaccession No. MN985325).

In alternative embodiments, the inactivated or attenuated causativeagent of the infection, or the live, viable or infectious causativeagent of the infection, is administered in unit dosages of between about10 to 50, or 1 to 20, trillion infectious units (or particles, ifattenuated), or between about one infectious unit to 10, 20 or 30billion infection units (or particles, if attenuated).

Hand-Held or Portable Devices

In alternative embodiments, provided are portable, for example,hand-held (or worn around the neck), medical devices, for example, aninhaler, ionizer, asthma puffer or nebulizer, capable of administeringan inhalation product comprising a composition or formulation asprovided herein or as described herein, for example, an inactivated orattenuated agent of the infection, or a live, viable or infectiouscausative agent of the infection with or without a vaccine or with orwithout an adjuvant, or with or without an antimicrobial drug, forexample, as described herein.

In alternative embodiments, a portable, for example, hand-held, medicaldevice, for example, inhaler, asthma puffer or nebulizer, as providedherein can administer ionized air or air comprising generated electronsand/or negatively-charged oxygen ions and/or positively-charged ions.

In alternative embodiments, a portable or hand-held medical device asprovided herein comprises a cassette, packette, interchangeable disk(for example, for holding a powder) or reservoir (optionally arefillable reservoir) in or on the product of manufacture, or aremovable cassette or packette, interchangeable disk (for example, forholding a powder) that can be inserted into a slot or port on theproduct of manufacture, or a separate reservoir or container operativelylinked or joined to the product of manufacture, that comprises a vaccineor or live or attenuated causative agent of invention or a formulationor a medication, for inhalation as provided herein for delivery to auser.

In alternative embodiments, provided is a modified hairdryer-typemedical device capable of having an adjustable temperature, adjustableair intake; a provision (or receptacle) for insertion of adrug-containing cassette (optionally providing or delivering acombination of medications, or the live or attenuated causative agentsand/or a vaccine as provided herein); and/or warm-to hot airavailability (optionally with temperature control) to inhibit viral andbacterial growth.

In alternative embodiments, a medical device as provided herein forinhalation delivery of a live or attenuated causative agent of infectionand/or a vaccine as provided herein drug or a medication or combinationsthereof to a user is fabricated as a meter-dose inhaler (MDI) (eitheropen or closed mouth MDI), which can comprise a pressurized canister ofthe drug or medication in a plastic case with a mouthpiece, and aholding chamber having a plastic tube with a mouthpiece, a valve tocontrol mist delivery and a soft sealed end to hold the MDI; the holdingchamber can assist delivery of the drug or medication to the nose and/orlungs, for example, as an AEROCHAMBER™ device.

In alternative embodiments, the inhaler or nebulizer is breathactivated, for example, as an REDIHALER™ device.

In alternative embodiments, a medical device as provided herein forinhalation delivery of a live or attenuated causative agent of infectionand/or a vaccine or a drug or a medication or combinations thereof to auser is fabricated a dry powder inhaler (such as a dry powder diskinhaler, for example, as a DISKUS™ device), optionally having a dosecounter window so user can see how many doses are left), for example,where the powder is dose dispensed by (using) a disposable, refillableor replaceable cassette, packette or disk; and the dry powder dispensingcan be breath activated, for example, as an AEROLIZER™, FLEXHALER™,PRESSAIR™, DISKUS™, HANDIHALER™, TWISTHALER™, ELLIPTA™, NEOHALER™,RESPICLICK™, ROTAHALER™ or TUBUHALER™ device.

In alternative embodiments, a medical device as provided herein forinhalation delivery of a live or attenuated causative agent ofinfection, or a vaccine or a drug or a medication or combinationsthereof, to a user is fabricated a nebulizer or soft mist inhaler, whichcan comprise a nebulizer delivery system comprising a nebulizer (forexample, a small plastic bowl with a screw-top lid) and a source forcompressed air to generate a mist comprising the drug or medication,which also can be dose dispensed using a disposable, refillable orreplaceable cassette, packette or disk.

In alternative embodiments, a medical device as provided herein forinhalation delivery of a live or attenuated causative agent ofinfection, or a vaccine or drug or a medication or combinations thereofto a user is fabricated a dry powder inhaler (such as a dry powder diskinhaler, for example, as a DISKUS™ device), optionally having a dosecounter window so user can see how many doses are left), for example,where the powder is dose dispensed by (using) a disposable, refillableor replaceable cassette, packette or disk; and the dry powder dispensingcan be breath activated, for example, as an AEROLIZER™, FLEXHALER™,PRESSAIR™, DISKUS™, HANDIHALER™, TWISTHALER™, ELLIPTA™, NEOHALER™,RESPICLICK™, ROTAHALER™ or TUBUHALER™ device.

Products of Manufacture and Kits

Provided are products of manufacture and kits for practicing methods asprovided herein; and optionally, products of manufacture and kits canfurther comprise instructions for practicing methods as provided herein.

Any of the above aspects and embodiments can be combined with any otheraspect or embodiment as disclosed here in the Summary, Figures and/orDetailed Description sections.

As used in this specification and the claims, the singular forms “a,”“an” and “the” include plural referents unless the context clearlydictates otherwise.

Unless specifically stated or obvious from context, as used herein, theterm “or” is understood to be inclusive and covers both “or” and “and”.

Unless specifically stated or obvious from context, as used herein, theterm “about” is understood as within a range of normal tolerance in theart, for example within 2 standard deviations of the mean. About (use ofthe term “about”) can be understood as within 20%, 19%, 18%, 17%, 16%,15%, 14%, 13%, 12% 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%,0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise clear fromthe context, all numerical values provided herein are modified by theterm “about.”

Unless specifically stated or obvious from context, as used herein, theterms “substantially all”, “substantially most of”, “substantially allof” or “majority of” encompass at least about 75%, 80%, 85%, 90%, 91%,92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99.5%, or more of a referencedamount of a composition.

The entirety of each patent, patent application, publication anddocument referenced herein hereby is incorporated by reference. Citationof the above patents, patent applications, publications and documents isnot an admission that any of the foregoing is pertinent prior art, nordoes it constitute any admission as to the contents or date of thesepublications or documents. Incorporation by reference of thesedocuments, standing alone, should not be construed as an assertion oradmission that any portion of the contents of any document is consideredto be essential material for satisfying any national or regionalstatutory disclosure requirement for patent applications.Notwithstanding, the right is reserved for relying upon any of suchdocuments, where appropriate, for providing material deemed essential tothe claimed subject matter by an examining authority or court.

Modifications may be made to the foregoing without departing from thebasic aspects of the invention. Although the invention has beendescribed in substantial detail with reference to one or more specificembodiments, those of ordinary skill in the art will recognize thatchanges may be made to the embodiments specifically disclosed in thisapplication, and yet these modifications and improvements are within thescope and spirit of the invention. The invention illustrativelydescribed herein suitably may be practiced in the absence of anyelement(s) not specifically disclosed herein. Thus, for example, in eachinstance herein any of the terms “comprising”, “consisting essentiallyof”, and “consisting of” may be replaced with either of the other twoterms. Thus, the terms and expressions which have been employed are usedas terms of description and not of limitation, equivalents of thefeatures shown and described, or portions thereof, are not excluded, andit is recognized that various modifications are possible within thescope of the invention.

A number of embodiments of the invention have been described.Nevertheless, it can be understood that various modifications may bemade without departing from the spirit and scope of the invention.Accordingly, other embodiments are within the scope of the followingclaims.

RELATED APPLICATIONS

This U.S. Utility Patent application claims the benefit of priorityunder 35 U.S.C. § 119(e) of U.S. Provisional Application Serial No.(USSN) 63/186,660, filed May 10, 2021; U.S. Ser. No. 63/188,311, May 13,2021; U.S. Ser. No. 63/214,997, Jun. 25, 2021; U.S. Ser. No. 63/223,427,Jul. 19, 2021; U.S. Ser. No. 63/241,485 filed Sep. 7, 2021; U.S. Ser.No. 63/253,813 filed Oct. 8, 2021; and, U.S. Ser. No. 63/273,069, filedOct. 28, 2021. The aforementioned applications are expresslyincorporated herein by reference in its entirety and for all purposes.

TECHNICAL FIELD

This invention generally relates to medicine and the medical treatmentof infections with vaccines, antibiotics and anti-viral drugs. Inalternative embodiments, provided are methods for treating,ameliorating, decreasing the chances of having any adverse effects from,decreasing the severity of adverse effects from, or preventing aninfection by administration of an antibiotic and/or an anti-viral drugsand a vaccine directed to a causative agent of the infection and/or aninactivated or attenuated causative agent of the infection, or a live,viable or infectious causative agent of the infection. In alternativeembodiments, the infection is bacterial, parasitic or viral. Inalternative embodiments, the viral infection is a coronavirus infectionsuch a Covid-19 or Covid-19 variant infection. In alternativeembodiments, methods as provided herein prevent or decrease theprevalence or severity of “vaccine breakthrough infections” aftervaccination, where mutants of the infection's causative agent developand infect patients in spite of the fact that they have undergoneimmunization, for example, to prevent a Covid-19 infection. Inalternative embodiments, methods as provided herein are used to preventin vivo mutations of an infectious agent to enhance to efficacy of anadministered vaccination; in other word, methods as provided herein areused to prevent in vivo replication of a viral infectious agent, andthus also prevents mutations of the viral infectious agent because wherethere is no replication of infectious agent there is no mutation ofinfectious agent. In alternative embodiments, methods comprisingadministration of a combination of an antiviral medication, drug ortreatment such as PF-07321332 or PAXLOVID™ and/or ritonavir and avaccine prevents acquisition of externally mutated viruses infecting thevaccinated person, as well as preventing replication in those possessingless effective neutralising antibodies to the mutants.

BACKGROUND

The process of immunization attempts to create immunity to preventacquisition of the new coronavirus or viruses. However, there is ongoingmutation occurring in the surrounding population because of ongoingreplication of viruses. Hence, “vaccine breakthrough” infections arebecoming reported, for example, see Hacisuleyman et al., New Eng J Med,Apr. 21, 2021. If the vaccine creates immunity to only the strains itwas created for, it may permit ‘reinfection’ with Covid-19 of a mutantstrain inhaled by the immunized person. This is termed “Vaccinebreakthrough’. Within the immunized person replication of an externalinfectious mutant can take place because the vaccine alone is inadequateto control the mutant replicating and the mutant strain may furthermutate in this seemingly safely immunized subject.

With COVID-19, there has been a rush into development of vaccines thatcould prevent the disease. However, the nature of this infection, beingan intracellular RNA type of virus, does not result in an easydevelopment of a vaccine. There are vaccines which work, for example,small pox, tetanus, polio, or measles, and there are conditions wherevaccines are of little use, for example, hepatitis C, humanimmunodeficiency virus (HIV) infection and tuberculosis (TB), and thenthere are vaccines which only give partial immunization and for a shortperiod of time, such as for example influenza virus immunization andmore recently malaria immunization attempts.

Currently used mRNA vaccines as well as non-mRNA vaccines aremanufactured by different companies such as Pfizer, AstraZeneca,Moderna, Johnson and Johnson (Janssen), Sputnik V, NovaVax, Sinovac,Sinopharm, Biological E, Valneva, EpiVac Corona, Convidiciae, Covaxinand others. All have been subject to various local side effects such asa swollen arm, systemic side effects such as fever, aches and pains,overwhelming feeling of doom, discomfort, profound tiredness and othersymptoms. A small percentage of patients develop thrombocytopenia andclotting which is reminiscent of disseminated intravascular coagulationas described by some, as well as neurologic, dermatologic, cardiac andother adverse effects.

The preventative success of mRNA vaccines has been reported to be up to90% or more. However, in real life experience data in some countries hasshown results of 50% to 90% efficacy. Some of these reduced efficacylevels may be due to mutants being present in that population. Unlessvaccine manufacturers can predict the development of specific mutations,which is virtually impossible, the vaccine market will always sufferfrom such reduced efficacy in various regions of the world.

Because of the ongoing mutations around the world of COVID-19, there aremultiple strains, including a current India strain, which has causedsuper-infections in patients who have been immunized, i.e., theso-called vaccine breakthrough phenomenon. The B.1.617 variant of theCovid-19, known more commonly as the double mutant strain, was firstdetected in India in October 2020. As the name suggests, the straininvolves two variants of the virus. The E484Q mutation hascharacteristics of a previously detected variant—the E484K—which wasseen in the fast-spreading Brazilian and South African variants, makingit highly transmissible. The L452R mutation, on the other hand, helpsthe virus evade the body's immune response. The double mutation strainwas subsequently named B.1.617

Yet it is clear that the virus had to replicate to mutate. Hence theadage “if it cannot replicate it cannot mutate”. Hence, one simplesolution to the problem of imperfect vaccine disease prevention is not abigger and better vaccine or multiple vaccinations because we will neverkeep up with the mutations. The best solution may well be prevention ofmutations. Yet it is clear that the virus had to replicate to mutate.And subsequently replicate in the immunized person. Hence the adage “ifit cannot replicate it cannot mutate”.

SUMMARY

In alternative embodiments, provided are methods for treating,ameliorating, decreasing the chances of having any adverse effects from,decreasing the severity of adverse effects from, or preventing aninfection, comprising administering to a subject or an individual inneed thereof, wherein optionally the individual in need thereof is ahuman or an animal:

-   -   (a) at least one antibiotic and/or anti-viral drug capable of        killing a causative agent of the infection, or completely or        partially inhibiting the ability of the causative agent of the        infection to replicate or become infectious or cause pathology        in the subject or the individual in need thereof; and,    -   (b) (i) at least one dose of a vaccine directed to the causative        agent of the infection upon entry into the vaccinated subject or        individual in need thereof,    -   wherein the vaccine is capable of initiating an immune response        in the individual that can substantially or partially kill or        neutralize a causative agent of the infection, or the vaccine        can completely, substantially or partially inhibit the ability        of the causative agent of the infection to replicate, or be        infectious, or cause pathology, in the subject or the individual        in need thereof, and/or    -   (ii) an inactivated or attenuated agent of the infection, or a        live, viable or infectious causative agent of the infection,        wherein optionally the live causative agent of the infection is        a completely or partially attenuated version of the causative        agent,    -   wherein at least one dosage of the at least one antibiotic        and/or anti-viral drug is administered 1, 2, 3, 4, 5, 6, 7, 8,        9, 10, 11, 12, 13 or 14 or more days before, or on the day of, a        first dose of the at least one of a plurality of dosages of the        vaccine is administered, or a dose of the inactivated,        attenuated, or the live, viable or infectious causative agent of        the infection.

In alternative embodiments, the causative agent of the infection is orcomprises a bacteria, protozoan or a virus, or the causative agent ofthe infection is or comprises the causative agent of:

-   -   a viral infection, optionally a coronavirus, a virus that causes        a common cold, an influenza virus (optionally an influenza A, B        or C), a hepatitis virus, a rous sarcoma virus (RSV), a        Paramyxoviridae or measles virus, a Paramyxovirus or mumps        virus, a Herpes simplex virus (HSV), a Cytomegalovirus (CMV), a        Rubivirus or rubella virus, an Enterovirus, a viral meningitis,        a rhinovirus, a human immunodeficiency virus (HIV), a        varicella-zoster or chickenpox virus, an Orthopoxvirus or        variola or smallpox virus, an Epstein-Barr virus (EBV), an        Adenovirus, a Hantavirus, a Flaviviridae or Dengue virus, a Zika        virus, or a chikungunya virus infection,    -   a coronavirus infection, optionally a COVID-19 or a COVID-19        variant infection, or a Middle East respiratory syndrome virus        (MERS-CoV) infection;    -   malaria caused by a parasite of the genus Plasmodium        (optionally P. vivax, P. falciparum, P. malariae, P. ovale,        or P. knowlesi);    -   dengue fever or dengue shock syndrome caused by a virus of the        Flaviviridae family or a dengue virus;    -   a Flaviviridae family virus infection or a hepatitis or a        hepatocellular carcinoma associated with viral hepatitis caused        by a virus of the Flaviviridae family or a virus of the genus        Hepacivirus or Hepacivirus C virus or hepatitis C;    -   filariasis, leprosy or streptocerciasis or an infection caused        by a parasite of the superfamily Filarioidea (optionally Brugia        malayi, Brugia timori, Wuchereria bancrofti, Loa loa, Mansonella        streptocerca, Mansonella ozzardi, or Mansonella perstans);    -   leprosy or an infection caused by a parasite of the genus        Mycobacterium (optionally M. leprae or M. lepromatosis);    -   river blindness or onchocerciasis caused by a parasitic worm or        a parasite of the genus Onchocerca (optionally O. volvulus);    -   a hookworm or a roundworm infection caused by a parasite of the        genus Ancylostoma (optionally A. duodenale or A. ceylanicum) or        Necator (optionally N. americanus);    -   trichuriasis or a whipworm infection caused by a parasite of the        genus Trichuris (optionally T. trichiura); roundworm or an        Ascaris infection that is caused by Ascaris lumbricoides;    -   scabies or a mite-carried infection caused by the parasite of        the genus Sarcoptes (optionally S. scabiei);    -   typhus or an infection caused by a lice or a parasite of the        order Phthiraptera (optionally Pediculus humanus capitis);    -   enterobiasis or an infection caused by a pinworm or a parasite        of the genus Enterobius (optionally E. vermicularis); and/or    -   pulicosis or an infection caused by a flea or an insect of the        order Siphonaptera or of the genus Pulex (optionally P.        irritans).

In alternative embodiments, the virus is an influenza virus or acoronavirus, optionally a COVID-19 virus.

In alternative embodiments, the at least one antibiotic and/oranti-viral drug comprises: an avermectin class drug (optionallyivermectin) alone; a combination of an avermectin class drug and anantibiotic, or a combination of an ivermectin and an antibiotic or anantiviral drug or therapeutic, optionally a combination of an avermectinclass drug, an antibiotic and zinc or a zinc salt, or a combination ofivermectin and an antibiotic and zinc or a zinc salt.

In alternative embodiments, the avermectin class drug comprises:ivermectin (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin(optionally milbemectin, milbemycin oxime, moxidectin or nemadectin),doramectin (optionally DECTOMAX™), eprinomectin or abamectin. Inalternative embodiments, the avermectin class drug is administered witha synthetic nucleoside analog or derivative, or N4-hydroxycytidine, or aprodrug of N4-hydroxycytidine, optionally molnuvpiravir (Merck), orfavipiravir (also known as T-705 or AVIGAN™, or favilavir, ToyamaChemical, Fujifilm, Japan, or FABIFLU™, Glenmark Pharmaceuticals).

In alternative embodiments, the antibiotic comprises an antibacterialantibiotic or a macrolide drug,

-   -   wherein optionally the macrolide drug comprises azithromycin,        optionally dosaged at between about 50 mg to about 2000 mg per        dose or per day (optionally, ZITHROMAX™, or AZITHROCIN™,        optionally an oral extended- or delayed-release formulation of        azithromycin, or ZMAX™), clarithromycin (optionally, BIAXIN™),        erythromycin (optionally, ERYTHROCIN™), or fidaxomicin        (optionally, DIFICID™ or DIFICLIR™), troleandomycin (optionally,        TEKMISIN™), tylosin (optionally, TYLOCINE™ or TYLAN™),        solithromycin (optionally, SOLITHERA™), oleandomycin (or        SIGMAMYCINE™), midecamycin, roxithromycin, kitasamycin or        turimycin, josamycin, carbomycin or magnamycin, and/or        spiramycin,    -   and optionally the antibacterial antibiotic comprises a        tetracycline class drug, a glycylcycline or a fluorocycline        class drug, or an analogue thereof, and optionally the        tetracycline, glycylcycline or fluorocycline drug or analogue        thereof comprises or is: tetracycline or SUMYCIN™;        chlortetracycline or AUREOMYCIN™; oxytetracycline;        demeclocycline or DECLOMYCIN™, DECLOSTATIN™, LEDERMYCIN™,        BIOTERCICLIN™, DEGANOL™, DETECLO™, DETRAVIS™, MECICLIN™,        MEXOCINE™, CLORTETRIN™; lymecycline; meclocycline; metacycline;        minocycline or MINOCIN™; rolitetracycline; doxycycline, or        DORYX™, DOXYHEXA™, DOXYLIN™; tigecycline or TYGACIL™;        eravacycline or XERAVA™; sarecycline or SEYSARA™; omadacycline        or NUZYRA™; or any combination thereof.

In alternative embodiments, the at least one antibiotic and/oranti-viral drug comprises a combination of ivermectin and doxycycline(optionally DORYX™, DOXYHEXA™, DOXYLIN™), optionally a combination ofivermectin, doxycycline and zinc or a zinc salt.

In alternative embodiments, the at least one antibiotic and/oranti-viral drug comprises a combination of ivermectin and azithromycinZITHROMAX™, or AZITHROCIN™, optionally an oral extended-releaseformulation of azithromycin, or ZMAX™), optionally a combination ofivermectin, azithromycin and zinc or a zinc salt.

In alternative embodiments, the at least one antibiotic and/oranti-viral drug comprises a combination of hydroxychloroquine(optionally, PLAQUENIL™) and azithromycin (optionally, ZITHROMAX™, orAZITHROCIN™, optionally an oral extended-release formulation ofazithromycin, or ZMAX™), optionally a combination of hydroxychloroquine,azithromycin and zinc or a zinc salt.

In alternative embodiments, the at least one antibiotic and/oranti-viral drug further comprises administration of a vitamin,optionally vitamin D and/or vitamin C.

In alternative embodiments, the zinc comprises: zinc sulphate, zincacetate, zinc gluconate or zinc picolinate or a zinc salt.

In alternative embodiments, on the day of administration of, or at leastone day after the first dose of: (a) the attenuated and/or the live,viable or infectious causative agent of the infection, and/or (b) thevaccine, is given, the individual in need thereof is administered moreof the at least one antibiotic and/or anti-viral drug, or a differentcombination of an least one antibiotic and/or anti-viral drug, or adifferent dosage of the at least one antibiotic and/or anti-viral drug.

In alternative embodiments, the individual in need thereof isadministered more of the at least one antibiotic and/or anti-viral drug,or a different combination of an least one antibiotic and/or anti-viraldrug, or a different dosage of the at least one antibiotic and/oranti-viral drug on day zero (the day of administration), or day 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 after administration of the firstdosage of the vaccine and/or the attenuated and/or the live, viable orinfectious causative agent of the infection.

In alternative embodiments, a booster, or at least one second orfollow-up administration of: at least one dosage of a vaccine and/or anattenuated and/or a live, viable or infectious causative agent of theinfection, is given between about 1 week to one year (or between abouttwo weeks to 9 months, or between about three weeks to 8 months, orbetween about one month to 7 months, or about 3, 4, 5, or 6 months)after the first administration of the at least one vaccine and/or theattenuated and/or the live, viable or infectious causative agent of theinfection,

-   -   and optionally, wherein on day zero, or at least one day, or        about two days, after, administration of the second or        additional or booster dose of the vaccine, and/or the attenuated        and/or the live, viable or infectious causative agent of the        infection, is given, the individual in need thereof is        administered more of the at least one antibiotic and/or        anti-viral drug, or a different combination of an least one        antibiotic and/or anti-viral drug, or a different dosage of the        at least one antibiotic and/or anti-viral drug.

In alternative embodiments, the individual in need thereof isadministered more of the at least one antibiotic and/or anti-viral drug,or a different combination of an least one antibiotic and/or anti-viraldrug, or a different dosage of the at least one antibiotic and/oranti-viral drug on day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14after administration of the second or additional or booster dose of thevaccine and/or the attenuated and/or the live, viable or infectiouscausative agent of the infection.

In alternative embodiments, the at least one antibiotic and/oranti-viral drug is repeatedly administered about every 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13 or 14 or more days for one or several weeks(optionally, 2, 3, 4, 5, or 6 weeks) until plasma ivermectin isdetectable.

In alternative embodiments, the vaccine is: a nucleic acid-basedvaccine, optionally an RNA vaccine or a DNA vaccine; a peptide orpolypeptide-based vaccine; or, the vaccine comprises an inactivatedvirus.

In alternative embodiments, the anti-bacterial and/or anti-viral drug ordrug combination, or the attenuated and/or the live, viable orinfectious causative agent of the infection, or the vaccine, isadministered orally or by inhalation, or the the anti-bacterial and/oranti-viral drug or drug combination or the attenuated and/or the live,viable or infectious causative agent of the infection is administered byinclusion in a liquid (optionally to be administered as a drink or indrops such as nasal drops or in a mist), a tablet, a capsule, a gel, ageltab, a powder, a lozenge, an aerosol, spray, or mist formulation thatis inhaled or administered nasally or orally (optionally, by a puffer ora nebulizer), or is formulated in a liquid (optionally the liquid is asterile saline) solution which is ingested or gargled by the individualin need thereof.

In alternative embodiments, the attenuated and/or the live, viable orinfectious causative agent of the infection is administered in unitdosages of between about 10 to 50 trillion infectious units orparticles, or between about one infectious unit or particle to 10, 20 or30 billion infection units or particles.

In alternative embodiments, after the first administration of (a) theattenuated and/or the live, viable or infectious causative agent of theinfection, and/or (b) the vaccine, the IgM, IgG and/or IgA levels in theindividual in need thereof is tested and measured (qualitatively and/orquantitatively), and optionally if levels of the measured IgM, IgGand/or IgA are low, a second or additional dosage or administration ofthe (a) the attenuated and/or the live, viable or infectious causativeagent of the infection, and/or (b) the vaccine, is given,

-   -   and optionally levels of the measured IgM, IgG and/or IgA are        measured at between about 7 to 21 days, or at 14 and 20 days,        after the first administration.

In alternative embodiments, the individual in need thereof is a human oran animal, and optionally the animal is a domestic, farm or zoo animal.

In alternative embodiments, the methods comprise administering incoordination with (optionally before, at the time of and/or aftervaccination of and/or administration of the attenuated and/or the live,viable or infectious causative agent of the infection) theanti-microbial (optionally antiviral) vaccine and/or the attenuatedand/or the live, viable or infectious causative agent of the infection,a therapeutic combination of drugs or a single drug, an antisera or anantibody, a pharmaceutical dosage form, a drug delivery device, or aproduct of manufacture, comprising:

-   -   (a) a thiazolide class drug, optionally nitazoxanide (or ALINIA™        NIZONIDE™) or tizoxanide (or        2-Hydroxy-N-(5-nitro-2-thiazolyl)benzamide);    -   (b) molnupiravir, optionally co-administered with and/or        formulated with an avermectin class drug (optionally        ivermectin), an antibiotic (optionally doxycycline or        azithromycin) and/or zinc, or co-administered with and/or        formulated with ivermectin, hydroxychloroquine, an antibiotic        (optionally doxycycline or azithromycin) and/or zinc;    -   (c) opaganib or YELIVA™, or opaganib or YELIVA™ and oral and/or        inhaled or aerosol chloroquine (or ARALEN™), chloroquine        phosphate, chloroquine diphosphate, amodiaquine (or AMDAQUINE™,        AMOBIN™) and/or hydroxychloroquine (optionally, PLAQUENIL™),        wherein optionally each or both of the opaganib and the        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        are in or formulated as a formulation for inhalation, for        example, formulated as an aerosol, spray, mist, liquid or        powder, or each or both are formulated for oral, intramuscular        or intravenous administration,    -   wherein optionally the opaganib is administered at a dosage of        QD (once a day), bid (twice a day) or tid (three times a day) at        a dosage of between about 100 to 600 mg per day or per dosage,        or at about 100, 200, 300, 400, 500 or 600 mg per day or per        dosage,    -   and optionally the opaganib, or YELIVA™ is also administered or        formulated with an antibiotic (optionally azithromycin or        doxycycline), ivermectin (optionally at 12 mg ivermectin,        optionally administered on days 1, 3, 6 and 8),        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc        (optionally zinc sulfate, optionally at (50 mg daily, or any        zinc salt);    -   (d) lopinavir, ritonavir (or NORVIR™) and oseltamivir        (optionally, TAMIFLU™), and/or zanamivir (or RELENZA™);    -   (e) lopinavir combined (formulated) with ritonavir (or NORVIR™),        or KALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or        LOPINAVIR™, and/or zanamivir (or RELENZA™), or lopinavir and        ritonavir separately formulated;    -   (f) lopinavir combined (formulated) with ritonavir (or NORVIR™)        (or KALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or        LOPINAVIR™), or lopinavir and ritonavir (or NORVIR™), and        oseltamivir (optionally, TAMIFLU™), and/or zanamivir (or        RELENZA™), optionally also with inhaled or aerosol formulations        or versions of chloroquine (or ARALEN™) amodiaquine (or        AMDAQUINE™, AMOBIN™), chloroquine phosphate, and/or oral        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        simultaneously;    -   (g) lopinavir, ritonavir (or NORVIR™), amodiaquine (or        AMDAQUINE™, AMOBIN™), chloroquine and oseltamivir (or TAMIFLU™);        wherein optionally the chloroquine comprises inhaled or aerosol        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        and/or oral chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) simultaneously;    -   (h) lopinavir and oseltamivir (optionally, TAMIFLU™), and/or        zanamivir (or RELENZA™);    -   (i) ritonavir (or NORVIR™) and oseltamivir (optionally,        TAMIFLU™), and/or zanamivir (or RELENZA™);    -   (j) remdesivir (optionally, GS-5734™, Gilead Sciences) alone, or        oseltamivir (optionally, TAMIFLU™) and remdesivir (optionally,        GS-5734™, Gilead Sciences), and optionally the remdesivir is an        oral formulation and/or an inhaled or aerosol remdesivir        formulation;    -   (k) oseltamivir (optionally, TAMIFLU™) and efavirenz        (optionally, SUSTIVA™), and/or zanamivir (or RELENZA™);    -   (l) oseltamivir (optionally, TAMIFLU™) and nevirapine (or the        combination efavirenz with emtricitabine and tenofovir, or        ATRIPLA™);    -   (m) oseltamivir (or TAMIFLU™) and amprenavir (optionally,        AGENERASE™);    -   (n) oseltamivir (optionally, TAMIFLU™) and nelfinavir        (optionally, VIRACEPT™);    -   (o) a thiazolide class drug, optionally nitazoxanide (optionally        ALINIA™, NIZONIDE™) or tizoxanide (or        2-Hydroxy-N-(5-nitro-2-thiazolyl)benzamide), with or in        combination with any of (a) to (hh), or any drug or drug        combination as provided herein, optionally a thiazolide class        drug, optionally nitazoxanide, with an avermectin class drug        such as ivermectin (optionally STROMECTOL™), moxidectin        (optionally CYDECTIN™, EQUEST™, QUEST™), selamectin (optionally        STRONGHOLD™), a milbemycin (optionally milbemectin, milbemycin        oxime, moxidectin or nemadectin), doramectin (optionally        DECTOMAX™), eprinomectin or abamectin; or a thiazolide class        drug (optionally, nitazoxanide or tizoxanide) and oseltamivir        (or TAMIFLU™),    -   and optionally the thiazolide class drug (optionally,        nitazoxanide or tizoxanide) is formulated or administered with        ribavirin or tribavirin (or COPEGUS™, REBETOL™, or VIRAZOLE™),        and an avermectin class drug such as ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin;    -   (p) plitidepsin (also known as dehydrodidemnin B), or APLIDIN™        (PharmaMar, S. A.);    -   (q) an inhibitor or S-phase kinase-associated protein 2 (SKP2),        or dioscin, or niclosamide, or NICLOCIDE™, FENASAL™, or        PHENASAL™;    -   (r) ribavirin or tribavirin (or COPEGUS™, REBETOL™, or        VIRAZOLE™) interferon beta 1b, or a combination of ribavirin and        interferon beta, or a combination of lopinavir and ritonavir (or        NORVIR™) and interferon-beta-1b;    -   (s) abacavir, acyclovir, or optionally ACICLOVIR™, adefovir,        amantadine, ampligen, amprenavir (optionally, AGENERASE™),        aprepitant, umifenovir (or ARBIDOL™), atazanavir, atripla,        balavir, baloxavir marboxil (XOFLUZA™), bepotastine, bevirimat,        bictegravir, a combination of bictegravir and emtricitabine and        tenofovir alafenamide (or BIKTARVY™), brilacidin, bivalirudin        (or BIVALITROBAN™), cidofovir, caspofungin, lamivudine and        zidovudine (optionally, COMBVIR™), cobicstat, colisitin,        cocaine, darunavir, delavirdine, descovy, didanosine, docosanol,        dolutegravir, ecoliever, edoxudine, efavirenz (optionally,        SUSTIVA™), elvitegravir, emtricitabine, enfuvirtide, entecavir,        epirubicin, epoprostenol, etravirine, famciclovir, fomivirsen,        fosamprenavi, foscarnet, fosfonet, galidesivir, ibacitabine,        icatibant, idoxuridine, ifenprodil, imiquimod, imunovir,        indinavir, inosine, an interferon (optionally interferon type I,        interferon type II and/or interferon type III), lamivudine (or        EPIVIR™, ZEFFIX™), lopinavir, loviride, ledipasvir, leronlimab,        maraviroc, methisazone, moroxydine, nelfinavir, nevirapine,        nexavir, nitazoxanide (optionally ALINIA™, NIZONIDE™), norvir, a        nucleoside analogue or derivative (optionally brincidofovir (or        TEMBEXA™), didanosine (or VIDEX™), favipiravir (also known as        T-705 or AVIGAN™, or favilavir, Toyama Chemical, Fujifilm,        Japan, or FABIFLU™, Glenmark Pharmaceuticals), vidarabine,        galidesivir (optionally, BCX4430, IMMUCILLIN-A™), remdesivir        (optionally, GS-5734™, Gilead Sciences), cytarabine,        gemcitabine, emtricitabine, lamivudine, zalcitabine, abacavir,        acyclovir, entecavir, stavudine, telbivudine, zidovudine,        idoxuridine and/or trifluridine or any combination thereof),        oseltamivir (or TAMIFLU™), peginterferon alfa-2a, penciclovir,        peramivir (optionally, RAPIVAB™), perfenazine, pleconaril,        plurifloxacin, podophyllotoxin, pyramidine, raltegravir,        rifampicin, ribavirin or tribavirin (or COPEGUS™, REBETOL™, or        VIRAZOLE™), rilpivirine, rimantadine, ritonavir (or NORVIR™)        saquinavir, sofosbuvir, stavudine, telaprevir, tegobuv,        tenofovir alafenamide, tenofovir disoproxil, tenofovir,        tipranavir, trifluridine, trizivir, tromantadine, truvada,        valaciclovir (optionally, VALTREX™), valganciclovir, valrubicin,        vapreotide, vicriviroc, vidarabine, viramidine, velpatasvir,        vivecon, zalcitabine, zanamivir (optionally, RELENZA™),        zidovudine, an immunosuppressive drug (optionally tocilizumab or        atlizumab, or ACTEMRA™, or ROACTEMRA™) or any combination        thereof;    -   (t) a mucolytic therapy or drug, optionally acetylcysteine,        ambroxol, bromhexine (or BISOLVON™), carbocisteine, erdosteine,        mecysteine or dornase alfa, or an expectorant, optionally        guaifenesin;    -   (u) a viral, or a coronavirus or a COVID-19, protease inhibitor,        optionally ASC09 (CAS registry no. 1000287-05-7) (Janssen        Research and Development, LLC), ritonavir (or NORVIR™) or ASC09        and ritonavir, or a JAK1/2 inhibitor (optionally baricitinib),        optionally compound 11r (University of Lubeck, Germany, see        optionally, Zhang et al J. Med Chem 2020, Feb. 11, 2020), or        darunavir, cobicistat or darunavir and cobicistat;    -   (v) an angiotensin-converting enzyme 2 (ACE2) inhibitor,        optionally to block the site of viral spike protein interaction        for anti-SARS-CoV-2 infection control;    -   (w) an anti-vascular endothelial growth factor (VEGF)        (optionally VEGF-A) drug or antibody, optionally bevacizumab;    -   (x) a protease inhibitor, optionally danoprevir, optionally a        serine protease inhibitor, optionally camostat or narlaprevir        (optionally ARLANSA™);    -   (y) anti-PD-1 checkpoint inhibitor, optionally camrelizumab;    -   (z) a compound or antibody capable of binding complement factor        C5 and blocking membrane attack complex formation, optionally        eculizumab;    -   (aa) a cathepsin inhibitor, optionally a cathepsin K, B or L        inhibitor, optionally relacatib;    -   (bb) thalidomide, or thalidomide and glucocorticoid (optionally        low-dose glucocorticoid), or and thalidomide and celecoxib;    -   (cc) an antibacterial antibiotic or a macrolide drug,    -   wherein optionally the macrolide drug comprises azithromycin,        optionally dosaged at between about 50 mg to about 2000 mg per        dose or per day (optionally, ZITHROMAX™, or AZITHROCIN™,        optionally an oral extended- or delayed-release formulation of        azithromycin, or ZMAX™), clarithromycin (optionally, BIAXIN™),        erythromycin (optionally, ERYTHROCIN™), or fidaxomicin        (optionally, DIFICID™ or DIFICLIR™), troleandomycin (optionally,        TEKMISIN™), tylosin (optionally, TYLOCINE™ or TYLAN™),        solithromycin (optionally, SOLITHERA™), oleandomycin (or        SIGMAMYCINE™), midecamycin, roxithromycin, kitasamycin or        turimycin, josamycin, carbomycin or magnamycin, and/or        spiramycin,    -   and optionally the antibacterial antibiotic comprises a        tetracycline class drug, a glycylcycline or a fluorocycline        class drug, or an analogue thereof, and optionally the        tetracycline, glycylcycline or fluorocycline drug or analogue        thereof comprises or is: tetracycline or SUMYCIN™;        chlortetracycline or AUREOMYCIN™; oxytetracycline;        demeclocycline or DECLOMYCIN™, DECLOSTATIN™, LEDERMYCIN™,        BIOTERCICLIN™, DEGANOL™, DETECLO™, DETRAVIS™, MECICLIN™,        MEXOCINE™, CLORTETRIN™; lymecycline; meclocycline; metacycline;        minocycline or MINOCIN™; rolitetracycline; doxycycline, or        DORYX™, DOXYHEXA™, DOXYLIN™; tigecycline or TYGACIL™;        eravacycline or XERAVA™; sarecycline or SEYSARA™; omadacycline        or NUZYRA™; or any combination thereof,    -   and optionally the antibacterial antibiotic or macrolide drug,        optionally azithromycin (or ZMAX™), is administered in        combination with, and/or is combined with, chloroquine (or        ARALEN™), amodiaquine (or AMDAQUINE™, AMOBIN™), chloroquine        phosphate, chloroquine diphosphate and/or hydroxychloroquine        (optionally, PLAQUENIL™), and the combination is administered        commencing on the first, second, third, fourth, fifth, sixth,        seventh, eighth, ninth and/or tenth day of therapy, or is        administered for 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 20 or more        days, or for between about 1 to 21 days or longer, or is        administered until within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or up to        20 or more days of ending the therapy for treating, preventing,        ameliorating, slowing the progress of, decreasing the severity        of or preventing the coronavirus infection,    -   and optionally the chloroquine (or ARALEN™), chloroquine        phosphate, amodiaquine (or AMDAQUINE™, AMOBIN™), chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        is administered the entire length of the treatment but the        azithromycin, optionally dosaged at between about 50 mg to about        2000 mg per dose or per day (optionally, ZITHROMAX™, or        AZITHROCIN™, optionally an oral extended-release formulation of        azithromycin, or ZMAX™) administration is halted or ceased after        two, three, four, five or six days after treatment is commenced,        and optionally the azithromycin administration is replaced by a        tetracycline class drug, and optionally the tetracycline class        drug comprises doxycycline, or DORYX™, DOXYHEXA™, DOXYLIN™        administration,    -   and optionally the antibacterial antibiotic, optionally        azithromycin (optionally, ZITHROMAX™, or AZITHROCIN™, optionally        dosaged at between about 50 mg to about 2000 mg per dose or per        day,    -   and optionally an oral extended-release formulation of        azithromycin, or ZMAX™), is administered or formulated with an        avermectin class drug such as ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin, and/or cholecalciferol (vitamin D3) or calcifediol,    -   and optionally the antibacterial antibiotic comprises an        antimycobacterial drug, and optionally the antimycobacterial        drug comprises clofazimine (optionally LAMPRENE™);    -   (dd) an avermectin class drug such as ivermectin (optionally        STROMECTOL™, SOOLANTRA™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin, optionally dosaged and/or administered at about 5        microgram/kg to about 1 gram (g) per day, optionally formulated        or administered at about 1 to 10, 12, 15, 20, 30, 40, 50, 60,        70, 80, 100, 120, 140, 160, 180, 200, 220 or 240 mg per day, or        between about 1 to 240 mg per day, or between about 3 to 240 mg        per day,    -   optionally formulated or administered with an antibiotic        (optionally azithromycin, minocycline, amoxicillin, niclosamide,        nitazoxanide, hydroxychloroquine or doxycycline, and optionally        the doxycycline is at between about 25 to 600 mg per dose or per        day, or at about 100 mg per dose or per day, and optionally the        azithromycin is at between about 50 mg to 2000 mg per dose or        per day), optionally as a single or a divided dose, and        optionally formulated and administered as an inhalant or a mist        (optionally using a nebulizer, nasal spray or equivalent),        optionally formulated as an aerosol, spray, mist, liquid or        powder, optionally formulated as an aerosol, spray, mist, liquid        or powder,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is formulated with and/or administered with        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        with or without zinc (optionally a zinc sulphate, acetate,        gluconate or picolinate or any zinc salt), and optionally this        combination is administered weekly, or every two week, or one        every 5 to 28 days, as a prophylactic,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is administered alone in the morning (AM), and an        antibiotic (optionally doxycycline) and/or a chloroquine        (optionally, ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        is administered in the afternoon and/or evening,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is administered alone for 1, 2, 3, 4, 5, 6, 7, 8,        9, 10 or up to 20 or more days, followed by administration of an        antibiotic (optionally doxycycline) for a corresponding period        of days, and optionally repeating the cycle of dosaging,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is formulated or administered with:        -   (i) at least one antibiotic (wherein optionally the            antibiotic is doxycycline(optionally, DORYX™, DOXYHEXA™,            DOXYLIN™) (optionally formulated or administered at a dosage            of between about 25 mg to 600 mg per dose or per day), or            azithromycin (optionally, ZITHROMAX™, or AZITHROCIN™,            optionally dosaged at between about 50 mg to about 2000 mg            per dose or per day, optionally an oral extended-release            formulation of azithromycin, or ZMAX™) (optionally            formulated or administered at a dosage of between an about            50 mg to 2000 mg);        -   (ii) chloroquine (or ARALEN™), chloroquine phosphate,            chloroquine diphosphate and/or hydroxychloroquine            (optionally, PLAQUENIL™) (optionally formulated or            administered at a dosage of between an about 10 mg to 2000            mg per day);        -   (iii) a zinc (optionally a zinc sulphate, acetate, gluconate            or picolinate or any zinc salt) optionally formulated or            administered at a dosage of between about 1 mg to 250 mg;            and/or        -   (iv) at least one vitamin, and optionally the at least one            vitamin comprises: vitamin C optionally formulated or            administered at a dosage of between about 500 to 5000            units (U) per dose, and/or Vitamin D (or cholecalciferol)            optionally formulated or administered at a dosage of between            about 3,000 to 100,000 units per day, or between about            10,000 to 50,000 units a day,        -   and optionally the avermectin class drug such as ivermectin            (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,            EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a            milbemycin (optionally milbemectin, milbemycin oxime,            moxidectin or nemadectin), doramectin (optionally            DECTOMAX™), eprinomectin or abamectin is administered or            formulated alone or in combination with any of the above (i)            to (iv) (for example, at least one antibiotic, chloroquine            (or ARALEN™) chloroquine phosphate, chloroquine diphosphate            and/or hydroxychloroquine (optionally, PLAQUENIL™), zinc or            any zinc salt and/or at least one vitamin are formulated            (and administered) as oral formulations (for example, as            tablets, capsules, powders, gels or geltabs), injectable            formulations, powders (for example, for inhalation or for            addition to an ingestible liquid) or liquids (for example,            for ingestion, infusion or injection);    -   (ee) chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) alone or with (or formulated with) or in combination        with any of (a) to (bb), or chloroquine, chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) and oseltamivir (or TAMIFLU™);    -   (ff) chloroquine (optionally, ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) alone or with:        -   (i) an avermectin class drug such as ivermectin (optionally            STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,            QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin            (optionally milbemectin, milbemycin oxime, moxidectin or            nemadectin), doramectin (optionally DECTOMAX™), eprinomectin            or abamectin, optionally at a dosage of between about 3 to            340 mg per day, or about 6 mg to 60 mg, or about 10 mg to 80            mg dosages, or about 12 to 50 mg dosages;        -   (ii) vitamin D, vitamin D2 (or ergocalciferol), vitamin D3            (or cholecalciferol) optionally at a dosage of between about            3,000 to 100,000 units per day, or between about 10,000 to            50,000 units a day, and/or        -   (iii) with (i) and (ii) and zinc (optionally a zinc            sulphate, acetate, gluconate or picolinate or any zinc salt)            optionally at a dosage of between about 1 mg to 250 mg,            or (iv) the combination of (iii) also with a tetracycline            class drug, wherein optionally the tetracycline class drug            comprises doxycycline, or DORYX™, DOXYHEXA™, DOXYLIN™,            optionally dosages at between about 25 mg to 600 mg per day            or per dose, optionally between about 100 mg to 500 mg, or a            between about 200 mg to 400 mg per dose or per day;    -   (gg) colchicine, or COLCRYS™, MITIGARE™, optionally administered        or dosaged at between about 0.5 mg to 20 mg, or about 1 mg to 15        mg, or about 3 mg to 10 mg, or about 4 mg to 6 mg, per day for a        period of between about 7 and 21 days, or about 14 days, and        optionally also administered or formulated with an antibiotic        (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily);    -   (hh) a corticosteroid or glucocorticoid class drug such as        ciclesonide (or ALVESCO™, OMNARIS™, OMNIAIR™, ZETONNA™ or        ALVESCO™) budesonide (optionally RHINOCORT™ or PULMICORT™),        prednisolone (or ORAPRED™), methyl-prednisolone, prednisone (or        DELTASONE™ or ORASONE™) or hydrocortisone (or CORTEF™), or a        selective estrogen receptor modulator (SERM), or toremifene (or        FARESTON™), or clomifene or clomiphene (or CLOMID™, SEROPHENE™),        wherein optionally the corticosteroid or glucocorticoid class        drug (optionally ciclesonide) is inhaled;    -   and optionally the corticosteroid class drug (for example        budesonide) is administered by inhalation, for example, in a        nebulized form, for example, between about 1 mg to 12 mg per day        of budesonide is administered by inhalation, or between about 6        to 80 mg per day of prednisolone is administered orally, or        between about 6 to 100 mg per day of prednisone is administered        orally, or between about 30 to 400 mg per day of hydrocortisone        is administered orally,    -   and optionally the corticosteroid class drug is formulated as a        powder or for administration in an inhaler or by nasal spray, or        for rectal administration,    -   and optionally the corticosteroid class drug (for example,        budesonide) is administered together with or in combination with        10 mg to 80 mg, an antibiotic (optionally azithromycin or a        tetracycline class drug,    -   wherein optionally the tetracycline class drug comprises        doxycycline, or DORYX™, DOXYHEXA™, DOXYLIN™), zinc or any zinc        salt and/or a vitamin (optionally vitamin D or calcifediol, D2        (or ergocalciferol), D3 (or cholecalciferol), C, E, B12, B6);    -   (ii) an anti-androgen drug, and optionally the anti-androgen        drug is bicalutamide, optionally CASODEX™, or dutasteride (or        AVODART™),        -   and optionally the anti-androgen drug is a nonsteroidal            anti-androgen (NSAA) or an androgen receptor (AR)            antagonist, and optionally the NSAA or AR antagonist            comprises proxalutamide (or its developmental name GT-0918)            (Suzhou Kintor Pharmaceuticals, Inc., a subsidiary of Kintor            Pharmaceutical Limited), or flutamide (or niftolide, or            EULEXIN™), or bicalutamide (or CASODEX™) or enzalutamide (or            XTANDI™),        -   and optionally the anti-androgen drug comprises a            5α-reductase inhibitor, and optionally the 5α-reductase            inhibitor comprises finasteride (or PROSCAR™, PROPECIA™, or            FINIDE™)        -   and optionally the anti-androgen drug, or NSAA, or            proxalutamide or bicalutamide, is administered together with            or in combination with an avermectin class drug such as            ivermectin (optionally STROMECTOL™), moxidectin (optionally            CYDECTIN™, EQUEST™, QUEST™), selamectin (optionally            STRONGHOLD™), a milbemycin (optionally milbemectin,            milbemycin oxime, moxidectin or nemadectin), doramectin            (optionally DECTOMAX™), eprinomectin or abamectin;        -   and optionally the anti-androgen drug, or NSAA, or            bicalutamide, proxalutamide, flutamide or niftolide,            bicalutamide, enzalutamide or dutasteride, is administered            at dosages of about 50 to 100 mg optionally administered            once, twice (BID), three times (TID) or four times a day, or            is administered at dosages of about 50 to 100 mg per day,        -   and optionally the anti-androgen drug, or NSAA, or            bicalutamide, proxalutamide, flutamide or niftolide,            bicalutamide, enzalutamide or dutasteride, is administered            with an avermectin class drug, or ivermectin, optionally            also administered with hydroxychloroquine, zinc and/or a            vitamin (optionally vitamin D (optionally vitamin D2, or            ergocalciferol, or Vitamin D3 or cholecalciferol, optionally            administered at about 1000 to 4000 ugm/day) or vitamin C, B            or A;

and optionally bicalutamide is administered together with or incombination with an avermectin class drug such as ivermectin (optionallySTROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™, QUEST™),selamectin (optionally STRONGHOLD™), a milbemycin (optionallymilbemectin, milbemycin oxime, moxidectin or nemadectin), doramectin(optionally DECTOMAX™), eprinomectin or abamectin,

-   -   and optionally bicalutamide is administered together with or in        combination with an avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin;    -   (jj) a hydrocortisone or cortisol (optionally CORTEF™,        SOLUCORTEF™), optionally hydrocortisone sodium succinate or        hydrocortisone acetate or dexamethasome (optionally DEXTENZA™,        OZURDEX™, NEOFORDEX™);    -   (kk) an alpha-ketoamide (α-ketoamide), wherein optionally the        alpha-ketoamide is a structure as described by Zhang et al, J.        Med. Chem. 2020, 63, 9, 4562-4578, or Meng et al Chem.        Sci. (2019) vol. 10, pg 5156 (optionally the structure KAM-2),    -   and optionally the alpha-ketoamide is formulated or administered        as an inhalant or a powder or mist, and optionally formulated or        administered with (optionally as an inhalant): an avermectin        class drug such as ivermectin (optionally STROMECTOL™),        moxidectin (optionally CYDECTIN™, EQUEST™, QUEST™), selamectin        (optionally STRONGHOLD™), a milbemycin (optionally milbemectin,        milbemycin oxime, moxidectin or nemadectin), doramectin        (optionally DECTOMAX™), eprinomectin or abamectin; an antibiotic        (optionally azithromycin or a tetracycline class drug, wherein        optionally the tetracycline class drug comprises doxycycline, or        DORYX™, DOXYHEXA™, DOXYLIN™); chloroquine (or ARALEN™),        chloroquine phosphate, chloroquine diphosphate and/or        hydroxychloroquine (optionally, PLAQUENIL™); zinc or any zinc        salt; remdesivir (optionally, GS-5734™, Gilead Sciences);        oseltamivir (or TAMIFLU™); and/or, hydrocortisone; or, any        combination thereof;    -   (ll) a compound, drug or formulation that decreases stomach acid        production or decreases stomach pH, wherein optionally the        compound, drug or formulation comprises famotidine, or PEPCID™,        and optionally the famotidine is administered at a dosage of        between about 10 to 60 mg per day, or between about 20 to 40 mg        per day, and optionally the famotidine is administered is        administered with: an avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin, and/or a tetracycline tetracycline class drug, and        optionally the tetracycline class drug comprises doxycycline, or        DORYX™, DOXYHEXA™, DOXYLIN™;    -   (mm) a dendrimer, optionally astodrimer sodium (Starpharma,        Melbourne, Australia);    -   (nn) an antihistamine class drug such as azelastine, or        ASTELIN™, OPTIVAR™, ALLERGODIL™, brompheniramine, fexofenadine        or ALLEGRA™, pheniramine or AVIL™, or chlorpheniramine;    -   (oo) a selective serotonin reuptake inhibitor (SSRI) class drug,        optionally fluvoxamine, or LUVOX™, FAVERIN™, FLUVOXIN™;    -   (pp) a nicotinic antagonist, a dopamine agonist or a        noncompetitive N-Methyl-d-aspartic acid or N-Methyl-d-aspartate        (NMDA) antagonist, wherein optionally the nicotinic antagonist,        dopamine agonist or noncompetitive NMDA antagonist is        1-adamantylamine or amantadine, or GOCOVRI™, SYMADINE™,        SYMMETREL™, optionally administered or dosaged at between about        50 mg to 150 mg, or about 100 mg, per day for a period of        between about 7 and 21 days, or about 14 days, and optionally        the nicotinic antagonist, dopamine agonist or noncompetitive        NMDA antagonist is also administered or formulated with an        antibiotic (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily),        and optionally the amantadine is formulated or administered at        100 mg per day for the first two days of treatment, which        optionally can then be elevated to 100 mg twice daily,        optionally for the next 10 days;    -   (qq) an immunosuppressive drug, wherein optionally the        immunosuppressive drug comprises tocilizumab or atlizumab, or        ACTEMRA™, or ROACTEMRA™, or a calcineurin inhibitor (CNI),        wherein the CNI comprises ciclosporin (or cyclosporine or        cyclosporin), or NEORAL™, or SANDIMMUNE™, or tacrolimus, or        PROTOPIC™, or PROGRAF™, and optionally the immunosuppressive        drug is also administered or formulated with an antibiotic        (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily),    -   and optionally the calcineurin inhibitor (CNI), wherein the CNI        comprises ciclosporin (or cyclosporine or cyclosporin) is        formulated combination of CNI (optionally cyclosporine) at a        dose of 3 mg/kg (180 mg daily) together with 12 mg ivermectin        once, and optionally also plus zinc 50 mg base and doxycycline        100 mg bid, optionally all for 10 days;    -   (rr) a protein kinase inhibitor, wherein optionally the protein        kinase inhibitor is a p38 mitogen-activated protein kinase        inhibitor, or ralimetinib, and optionally the protein kinase        inhibitor is also administered or formulated with an antibiotic        (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily);    -   (ss) an anti-inflammatory therapy or at least one        anti-inflammatory therapy drug, wherein optionally the        anti-inflammatory therapy or drug comprises: a sphingosine        kinase-2 (SK2) selective inhibitor (optionally, opaganib        (optionally, YELIVA™), sirolimus, a JAK1/2/TYK2 inhibitor        (optionally ruxolitinib), an anti-CD47 mAb (optionally        meplazumab), a cyclooxygenase (COX) (optionally, COX2)        inhibitor, a glucocorticoid (optionally a synthetic        glucocorticoid, hydrocortisone, dexamethasone (or DEXTENZA™,        OZURDEX™, or NEOFORDEX™) or cortisol, or CORTEF™) or ciclesonide        (or ALVESCO™, OMNARIS™, OMNIAIR™, ZETONNA™ or ALVESCO™),        plitidepsin or dehydrodidemnin B, or APLIDIN™, or a nonsteroidal        anti-inflammatory drug (NSAID), wherein optionally the NSAID        comprises indomethacin (or indomethacin) or INDOCID™ or        INDOCIN™, or naproxen, or NAPROSYN™ or ALEVE™, or a        cyclooxygenase inhibitor, or a COX-1 or an COX-2 inhibitor, or        aspirin, or ibuprofen or ADVIL™ MOTRIN™ or NUROFEN™, or        celecoxib or CELEBREX™, or parecoxib or DYNASTAT™, or etoricoxib        or ARCOXIA™    -   and optionally the anti-inflammatory therapy or        anti-inflammatory therapy drug is also administered or        formulated with an antibiotic (optionally azithromycin or        doxycycline), ivermectin, hydroxychloroquine (optionally,        PLAQUENIL™) and/or zinc or any zinc salt (optionally zinc        sulfate, optionally at (50 mg daily),    -   and optionally opaganib, or YELIVA™, or opaganib, or YELIVA™        administered or formulated together with an oral and/or inhaled        or aerosol chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™)    -   and optionally the opaganib or YELIVA™ is formulated or        administered at a dosage of QD (once a day), bid (twice a day)        or tid (three times a day) at a dosage of between about 100 to        600 mg per day or per dosage, or at about 100, 200, 300, 400,        500 or 600 mg per day or per dosage,    -   and optionally the opaganib, or YELIVA™ is also administered or        formulated with an antibiotic (optionally azithromycin or        doxycycline), ivermectin (optionally at 12 mg ivermectin,        optionally administered on days 1, 3, 6 and 8),        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily);    -   (tt) a calcium channel blocker, or verapamil (or ISOPTIN™,        CALAN™), or a voltage gated potassium (KCNH2) channel or a        voltage gated calcium channel (CACNA2D2) blocker, or amiodarone        (or CORDARONE™, NEXTERONE™);    -   (uu) suramin, or ANTRYPOL™, BAYER 305™, or GERMANIN™;    -   (vv) a peroxisome proliferator-activated receptor (PPAR)        agonist, wherein optionally the PPAR agonist comprises        fenofibrate, or TRICOR™, FENOBRAT™, FENOGLIDE™, or LIPOFEN™, or        a combination of fenofibrate and simvastatin, or CHOLIB™,        optionally the PPAR agonist comprises a combination of        fenofibrate and pravastatin, or PRAVAFENIX™, or the PPAR agonist        comprises bezafibrate, or BEZALIP™, or combination of        bezafibrate and chenodeoxycholic acid, or HEPACONDA™, or        aluminium clofibrate, or alfibrate, or ciprofibrate, or        clinofibrate or LIPOCLIN™, or clofibrate or ATROMID-S™, or        clofibride, or gemfibrozil or LOPID™, or ronifibrate, or        simfibrate or CHOLESOLVIN™, or any combination thereof,    -   (ww) a synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or a prodrug of N4-hydroxycytidine,        optionally molnuvpiravir (Merck), or favipiravir (also known as        T-705 or AVIGAN™, or favilavir, Toyama Chemical, Fujifilm,        Japan, or FABIFLU™, Glenmark Pharmaceuticals),    -   wherein the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is given as between        about 10 mg to 3 gm per dose, or between about 10 mg to 3 gm per        day, or can be dosed either as a single dose or given one, two,        three or four times a day, or is administered at 200 to 800 mg        twice daily, or 200, 400, 600 or 800 mg twice daily, or at 200        to 800 mg three times a day, or at 200, 400, 600 or 800 mg three        times a day, or is administered at 200 to 800 mg three times a        day for between about 2 to 15 days, or for about 2, 3, 4, 5, 6,        7, 8, 9, 10, 11 or 12 days, and optionally when combined with        other drugs a lower dosage is used, optionally administered at        100 or 200 mg three times a day for between about 5 to 15 days,        or for about 7, 8, 9, 10, 11 or 12 days,    -   and optionally the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is administered with an        avermectin class drug (optionally ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin),    -   and optionally the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is administered with an        avermectin class drug (optionally ivermectin) with an        antibiotic, and optionally the antibiotic comprises        azithromycin, minocycline, amoxicillin, niclosamide,        nitazoxanide, hydroxychloroquine or doxycycline), and optionally        the synthetic nucleoside analog or derivative, avermectin class        drug, and antibiotic are administered together or as separate        formulations, and optionally are administered every one, two,        three, four or five weeks for between about one month and one        year or more;    -   and optionally molnuvpiravir, ivermectin and hydroxychloroquine        are administered together or as separate formulations, and        optionally are administered every one, two, three, four or five        weeks for between about one month and one year or more;    -   and optionally the synthetic nucleoside analog or derivative        (optionally N4-hydroxycytidine, or the prodrug of        N4-hydroxycytidine, optionally molnuvpiravir or favipiravir),        and antibiotic (optionally doxycycline or hydroxychloroquine) is        administered with zinc (optionally a zinc sulphate, acetate,        gluconate or picolinate, or zinc oxide nanoparticles, optionally        at a dosage of between about 1 mg to 250 mg, or about 50 mg per        day) and/or a vitamin, optionally vitamin C or D),    -   and optionally the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is administered with an        antibiotic (optionally the antibiotic comprises azithromycin,        minocycline, amoxicillin, niclosamide, nitazoxanide,        hydroxychloroquine or doxycycline), optionally also administered        with zinc (optionally a zinc sulphate, acetate, gluconate or        picolinate, or zinc oxide nanoparticles, optionally at a dosage        of between about 1 mg to 250 mg, or about 50 mg per day) and/or        a vitamin, optionally vitamin C or D,    -   and optionally any of these combinations is administered very 2,        3, 4, 5, 6, 7, 8, 9 or 10 or more days for between about 1 month        and one year or more;    -   (xx) an antisera or an antibody or antibody or vaccine therapy        for treating, preventing or ameliorating a microbial or a viral        infection (optionally a coronavirus infection, optionally a        COVID-19 infection) or a microbial infection (optionally a        protozoan, helminthiasis, insect and/or parasitic infection),        and optionally the antibody comprises a monoclonal antibody, and        optionally the monoclonal antibody comprises sotrovimab        (GlaxoSmithKline and Vir Biotechnology), or casirivimab,        imdevimab or casirivimab and imdevimab (REGEN-COV™) (Regeneron),        or bamlanivimab oretesevimab or bamlanivimab and etesevimab        (Junshi Biosciences), or tocilizumab or ACTEMRA™ or ROACTEMRA™        (Hoffmann-La Roche), and optionally the vaccine comprises        tozinamera or COMIRNATY™ (Pfizer), or elasomeran or SPIKEVAX™        (Moderna), or SPUTNIK V™ or Gam-COVID-Vac (Gamaleya Research        Institute), or AZD1222 or COVISHIELD™ or VAXZEVRIA™        (Oxford-AstraZeneca),    -   and optionally the antibody or antibody therapy comprises or is        contained in a convalescent sera or plasma, and/or    -   (yy) any combination of (a) to (xx),    -   and optionally any one or several or all of (a) to (yy) with an        (or formulated with or formulated as an) inhaled or aerosol        formulation such as a powder or a mist or aerosol, and/or        formulated with or formulated as an oral, intramuscular (IM) or        intravenous (IV) formulation, wherein optionally both the        inhaled (or aerosol) and the oral, IV and/or IM formulations are        administered simultaneously or sequentially,    -   and optionally the inhaled or aerosol formulation comprises        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        and/or oral chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) administered simultaneously or overlapping,    -   and optionally the inhaled or aerosol formulation comprises an        avermectin class drug such as ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin,    -   and optionally any one or several or all of (a) to (yy), or any        therapeutic combination of drugs or a drug, or a pharmaceutical        dosage form as provided herein, are administered orally,        intramuscularly, subcutaneously, topically, by use of an enema,        intravaginally, or intravenously, or administration is by        subcutaneous administration, sublingual administration,        inhalation or by aerosol (optionally by inhalation of a liquid,        an aerosol, a spray, a mist or a powder), by absorbable patch,        by use of an implant, or by use of an enema or a suppository.

In alternative embodiments, the anti-viral drug or medication, oranti-microbial drug, is or comprises: molnupiravir, efavirenz(optionally, SUSTIVA™), tenofovir, emtricitabine and tenofovir,nevirapine (or the combination efavirenz with emtricitabine andtenofovir, or ATRIPLA™), amprenavir (optionally, AGENERASE™), nelfinavir(optionally, VIRACEPT™) and/or remdesivir (optionally, GS-5734™, GileadSciences), a viral RNA-dependent RNA polymerase inhibitor, optionallygalidesivir,

-   -   and optionally the anti-viral drug or medication is or comprises        an anti-retroviral drug or drug combination, and optionally the        anti-retroviral drug or drug combination comprises: darunavir        and cobicistat (optionally, REZOLSTA™ or PREZCOBIX™); atazanavir        (or REYATAZ™) and cobicistat (or EVOTAZ™); a nucleoside analog        reverse-transcriptase inhibitor (NRTI) (optionally abacavir, or        ZIAGEN™), lamivudine and dolutegravir (TRIUMEQ™); tenofovir (or        disoproxil or emtricitabine) and elvitegravir and cobicistat        (optionally, STRIBILD™); tenofovir (or disoproxil or        emtricitabine) and elvitegravir and cobicistat (COMPLERA™ or        EVIPLERA™); molnupiravir, efavirenz (optionally, SUSTIVA™),        emtricitabine and tenofovir (ATRIPLA); lamivudine, nevirapine        and stavudine (optionally, TRIOMUNE™); atazanavir (or REYATAZ™)        and cobicistat (optionally, EVOTAZ™); lamivudine and raltegravir        (optionally, DUTREBIS™); lamivudine and dolutegravir (or        DOVATO™); doravirine, lamivudine and tenofovir (optionally,        DELSTRIGO™); or lamivudine, zidovudine and nevirapine        (optionally, CUOVIR-N™);    -   and optionally the additional anti-viral drug or medication, or        anti-microbial drug, is formulated with the chloroquine        (optionally, ARALEN™), chloroquine phosphate, chloroquine        diphosphate, hydroxychloroquine (optionally, PLAQUENIL™),        lopinavir, ritonavir (or NORVIR™) and/or oseltamivir or is        formulated separately from the chloroquine (optionally,        ARALEN™), chloroquine phosphate, chloroquine diphosphate,        hydroxychloroquine (optionally, PLAQUENIL™), lopinavir,        ritonavir (or NORVIR™) and/or oseltamivir,    -   and optionally the anti-viral drug or medication, or        anti-microbial drug, or palliative agent comprises or further        comprises: magnesium (Mg, optionally administer        intravenously (IV) to maintain a blood concentration of between        about 2.0 and 2.4 mmol/1); zinc or any zinc salt (optionally a        zinc sulphate, acetate, gluconate or picolinate, optionally        administered at about 75 to 100 mg/day or at a dosage of between        about 1 mg to 250 mg); at least one vitamin, wherein optionally        the at least one vitamin comprises vitamin K, vitamin D or        calcifediol (optionally D2 (or ergocalciferol) or Vitamin D3 or        cholecalciferol), optionally administered at about 1000 to 4000        ugm/day), vitamin B6 (or pyridoxine), vitamin B12, vitamin E,        and/or vitamin C (optionally administered at 500 mg bid); a        flavonoid, plant flavonol or quercetin optionally administered        at between about 250 to 500 mg bid; atorvastatin, or LIPITOR™,        SORTIS™ (optionally administered at between about 40 mg/day to        80 mg/day); or, melatonin, or CIRCADIN™, SLENYTO™ (optionally        between about 6 to 12 mg a day, optionally, at night), any of        which are optionally given enterally or parenterally.

In alternative embodiments, provided are kits comprising a vaccineand/or an attenuated and/or live causative agent of infection, and atleast one antibiotic and/or anti-viral drug capable of killing acausative agent of the infection, or completely or partially inhibitingthe ability of the causative agent of the infection to replicate orbecome infectious or cause pathology in an individual, as describedherein or used in any method as provided herein, wherein optionally thekit comprises instructions for practicing a method as provided herein.

In alternative embodiments of methods and kits as provided herein, the

-   -   (i)        1R,2S,5S)-N-[(1S)-1-cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl]-3-[(2S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide,        or a compound having the following structure and molecular        weight:

-   -   or stereoisomer, or enantiomer, or deuterated version thereof,        and    -   (ii) ritonavir,    -   are formulated together, or separately, and optionally are        formulated together or separately in or as a liquid (optionally        to be administered as a drink or in drops, optionally as nasal        drops or in a mist), a tablet, a capsule, a gel, a geltab, a        powder, a lozenge, an aerosol or spray.

In alternative embodiments of methods and kits as provided herein, theanti-viral drug combination is formulated in or as a pharmaceuticaldosage form, optionally formulated to be administered orally,intramuscularly, subcutaneously, topically, by use of an enema,intravaginally, or intravenously, or formulated for subcutaneousadministration, sublingual administration, inhalation or by aerosol(optionally by inhalation of a liquid, an aerosol, a spray, a mist or apowder), by absorbable patch, by use of an implant, or by use of anenema or a suppository.

In alternative embodiments of methods and kits as provided herein, the

-   -   (a)        1R,2S,5S)-N-[(1S)-1-cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl]-3-[(2S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide,        or a compound having the following structure and molecular        weight:

-   -   or stereoisomer, or enantiomer, or deuterated version thereof,        and/or    -   (b) ritonavir,    -   is or are administered:    -   (a) at a dosage of QD (once a day), bid (twice a day) or tid        (three times a day) at a dosage of between about 100 to 600 mg        per day or per dosage, or at about 100, 200, 300, 400, 500 or        600 mg per day or per dosage, or    -   (b) at a dosage of between about 10 mg to 3 gm per dose, or        between about 10 mg to 3 gm per day, or 12 mg or 3 mg/kg orally        twice daily, or 125 mg orally twice daily or 520 mg/130 mg        solution twice per day (optionally administered with efavirenz,        fosamprenavir, nelfinavir, or nevirapine), or    -   (c) is dosed either as a single dose or given one, two, three or        four times a day, or    -   (d) at 200 to 800 mg twice daily, or 200, 400, 600 or 800 mg        twice daily, or at 200 to 800 mg three times a day, or at 200,        400, 600 or 800 mg three times a day, or is administered at 200        to 800 mg three times a day for between about 2 to 15 days, or        for about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 days,    -   (e) for pediatric patients dosage at 16 mg or 4 mg/kg orally        twice daily, or    -   (f) when combined with other drugs a lower dosage, optionally        administered at 100 or 200 mg three times a day for between        about 5 to 15 days, or for about 7, 8, 9, 10, 11 or 12 days.

The details of one or more exemplary embodiments of the invention areset forth in the description below. Other features, objects, andadvantages of the invention will be apparent from the description, andfrom the claims.

All publications, patents, patent applications cited herein are herebyexpressly incorporated by reference in their entireties for allpurposes.

DETAILED DESCRIPTION

In alternative embodiments, provided are methods for treating,ameliorating, decreasing the chances of having any adverse effects from,decreasing the severity of adverse effects from, or preventing aninfection in an individual in need thereof, including humans andanimals, by administration of an antibiotic and/or an anti-viral drugsand a vaccine directed to a causative agent of the infection, and/or aninactivated or attenuated causative agent of the infection, or the live,viable or infectious causative agent of the infection. In alternativeembodiments, the infection (or causative agent of the infection) isparasitic, bacterial or viral. In alternative embodiments, the viralinfection is a coronavirus infection such a Covid-19 infection.

In alternative embodiments, methods as provide herein prevent ordecrease the prevalence or severity of “vaccine breakthrough infections”after vaccination, where external mutants of the infection's causativeagent develop and infect or re-infect patients in spite of the fact thatthey have undergone immunization, for example, to prevent a Covid-19infection. Thus, in alternative embodiments, methods as provided hereincomprise combining an effective anti-microbial (for example anti-viral)treatment (for example, a drug or a mixture of drugs or othertherapeutics) with an anti-microbial vaccine to prevent in vivomutations (and thus also prevent a vaccine breakthrough infection) of aninfectious agent such as virus, for example, a coronavirus such asCOVID-19 or variant thereof.

In alternative embodiments, methods as provide herein provide a solutionto the problem of imperfect vaccine disease prevention, where a biggerand/or better vaccine or multiple vaccinations are ineffective becausescience will never keep up with the continuing viral mutations. Inalternative embodiments, methods as provide herein prevent replicationof newly-inhaled mutants in the already vaccinated or ‘about to bevaccinated’ population.

In alternative embodiments, methods as provide herein comprise an addedanti-replication method of treatment in addition to vaccination toprotect the immunized population from mutants entering, replicating, andfurther mutating in the immunized population. In alternativeembodiments, methods as provide herein prevent replication and thusprevent an ongoing viral mutation, a method utilized by the mutant toescape neutralizing antibodies and destruction. No replication, nomutation.

In alternative embodiments, methods as provide herein comprise combiningan effective anti-microbial (for example anti-viral) treatment (forexample, a drug or a mixture of drugs or other therapeutics) with ananti-microbial vaccine such as a DNA vaccine such as an adenovirus-basedvaccine, an mRNA vaccine, a peptide-based vaccine, an inactivatedpathogen-based vaccine, and/or an vaccine manufactured by:

-   -   Sanofi (optionally VAT00002 or VAT00008),    -   GlaxoSmithKline,    -   Takeda Pharmaceutical (optionally TAK-019),    -   Pfizer (optionally tozinamera or COMIRNATY™),    -   Moderna (optionally elasomeran or SPIKEVAX™)    -   Novavax (optionally vaccine to SARS VLPs S protein and influenza        M1 protein),    -   CanSino Biologics,    -   Inovio,    -   Sinovac,    -   BioNTech,    -   Johnson and Johnson,    -   Valneva (France) and Dynavax Technologies (optionally VLA2001        and VLA2101),    -   Sinopharm (or China National Pharmaceutical Group Corporation),    -   Emergent BioSolutions (optionally human polyclonal hyperimmune        serum with antibodies to SARS-CoV-2),    -   Bharat Biotech (optionally COVAXIN®),    -   The Rockefeller University (optionally vaccine toMVA S alone, or        MVA-S prime and Ad5-S boost),    -   Helmholtz Centre for Infection Research; Technical University        Munich; German Center for Environmental Health (optionally        vaccine to NC protein add-mixed with MALP-2 by intranasal route        and boosting with MVA-NC by intramuscular route),    -   University of Manitoba; University of Pennsylvania School of        Medicine; Southern Research Institute; Fox Chase Cancer        Institute (optionally vaccine to Heterologous Adenoviral prime        boost AdHu5 s AdC7-nS),    -   University of North Carolina at Chapel Hill, USA (optionally        vaccine to VEEV replicon particles expressing the SARS-CoV S),    -   National Institute of Infectious Diseases, Japan (optionally        vaccine to recombinant D1 expressing S protein),    -   Beijing Institute of Genomics, China (optionally vaccine to        Recombinant trunctuated S—N fusion protein),    -   Saitama Medical University; Josai University; Nippon Oil and Fat        Corporation; National Institute of Infectious Diseases, Japan        (optionally vaccine to recombinant peptide N223 on liposomes),    -   Chinese Center for Disease Control and Prevention; Canadian        Science Centre for Human and Animal Health (optionally vaccine        to Recombinant TM-truncated S protein),    -   HKU-Pasteur Research Centre; The University of Hong Kong;        National Institutes of Health; Centers for Disease (optionally        vaccine to Trimeric Spike protein),    -   Sun Yat-sen University, China (optionally vaccine to SARS S DNA        prime and HLAA*0201 restricted peptides boost vaccine),    -   State Key Laboratory of Virology; Graduate University of Chinese        Academy of Sciences (optionally vaccine to or as a 3a DNA        vaccine),    -   Institute of ImmunoBiology, Shanghai Medical College of Fudan        University, China (optionally vaccine to DNA prime—protein        S437-459 and M1-20),    -   CNB-CSIC; University of Iowa (optionally vaccine to rSARSCoV-E),    -   International Vaccine Institute (IVI) (optionally vaccine to        recombinant adenovirus expressing truncated S protein (rADV-S)),    -   University Health Network, Canada, and United States Center for        Disease Control and Prevention (CDC) (optionally vaccine to        recombinant measles virus spike protein),    -   Institut Pasteur (optionally vaccine to MV-SARS recombinant        measles virus vaccine expressing SARS CoV antigen),    -   Baylor College Medicine; Sabin; New York Blood Center (NYBC);        University of Texas Medical Branch (UTMB); Walter Reed Army        Institute of Research (WRAIR); National Institute of Allergy and        Infectious Diseases (NIAID) (optionally vaccine to receptor        binding domain (RBD) of the SARS-CoV spike (S) protein),    -   Vaxine Pty Ltd, Australia (optionally vaccine to SARS        recombinant spike protein plus delta inulin),    -   Gamaleya Research Institute (optionally SPUTNIK V™ or        Gam-COVID-Vac), and/or    -   Oxford-AstraZeneca (optionally AZD1222 or COVISHIELD™ or        VAXZEVRIA™)    -   and others, including anti-COVID-19 vaccines.

Hence, methods as provided herein that combine antibiotic,anti-parasitic and/or anti-viral treatment with an inactivated orattenuated causative agent of an infection, or a vaccine or a live,viable or infectious causative agent of the infection (for example, alive or attenuated virus) administration, can treat, ameliorate orprevent a vaccine-breakthrough infection, as well as eradicating theinfection if present pre-vaccination enhance protection and eradicateinfection.

In alternative embodiments, methods as provide herein compriseadministering in coordination with (for example, before, during and/orafter) an anti-causative agent vaccination, or an anti-viralvaccination, and/or the inactivated or attenuated causative agent of theinfection, or the live, viable or infectious causative agent of theinfection (such as a live or attenuated virus) administration, any oneor combination of anti-viral, anti-parasitic or anti-bacterialtherapies, for example, one or more anti-COVID-19 infection medicationsor drugs, including for example, the drug ivermectin, or the combinationof ivermectin and an antibiotic with anti-viral properties such asdoxycycline or azithromycin, for example the combination of ivermectinand doxycycline or azithromycin, or the combination ivermectin anddoxycycline or azithromycin and zinc or any zinc salt (an anti-viralmineral, for example, and anti-COVID-19 mineral), which optionally alsocan be administered in conjunction or coordination with a vitamin orvitamins such as vitamin D and/or vitamin C.

In alternative embodiments, a drug combination administered incoordination with a vaccine and/or the inactivated or attenuatedcausative agent of the infection, or the live, viable or infectiouscausative agent of the infection (optionally a live or attenuated virus)administration comprises the commencement, optionally orally or byinhalation, of the antiviral combination before, or just before, and/orthe day (day zero) the vaccine and/or the inactivated or attenuatedcausative agent of the infection, or the live, viable or infectiouscausative agent of the infection (such as a live or attenuated virus)administration is given. For example, in alternative embodiments, thepatient (or individual in need thereof) is given a pre-vaccine drug oranti-viral treatment for between about 1 to 10 days, or between about 2to 21 days, depending on dosing and conditions. If the patient isalready infected but asymptomatic, because of this pre-vaccination (orpre-administration of the attenuated and/or the live infectiouscausative agent) treatment the patient will be free, or substantiallyfree, of the infection but not yet endowed with complete or partialimmunity. In other words, because of this pre-vaccination treatmentthere will be no virus, or substantially no virus, to replicate in vivoafter the anti-viral treatment. After administration of theanti-microbial drug or treatment (optionally, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13 or 14 or more days after a first anti-microbial drug ortreatment is first administered) the vaccine is given (depending on thetype of vaccine, this may be the first of a two or three injectionprocess). In alternative embodiments, after the first dose of thevaccine or the inactivated or attenuated causative agent of theinfection, or the live, viable or infectious causative agent of theinfection is given, the patient is treated at day 14 (or, optionally, onday 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14) with an antibioticor antiviral, for example, with a single preventative ivermectin andantibiotic drug combination (for example, using an antibiotic withanti-viral activity such as doxycycline or azithromycin), or ivermectinand doxycycline drug combination, or ivermectin and doxycycline and zincdrug combination, or ivermectin and azithromycin and zinc or any zincsalt, or any of these combinations with additional drugs or agent oradjuncts such as one or more vitamins, for example, vitamin B, C and/orD. In alternative embodiments, the drug combination administration isrepeated every 14 days (or, optionally, every 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13 or 14 or more days) for several weeks until plasmaivermectin is detectable over the 14 days. In alternative embodiments,later, the drug combination administration is repeated every 1, 2, 3, 4,5 or 6 weeks or more.

In alternative embodiments, a second dose of the vaccine and/or theinactivated or attenuated causative agent of the infection, or the live,viable or infectious causative agent of the infection, and optionallysubsequent boosters, are carried out between the intermittent (forexample, every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or up to 28days) anti-microbial (for example, anti-viral) doses.

In alternative embodiments, combining vaccine or the inactivated orattenuated causative agent of the infection, or the live, viable orinfectious causative agent of the infection with initial thenintermittent anti-microbial (for example, anti-viral) administrations asprovided herein achieves:

-   -   virtual 100%, or substantial (for example, 95% or more)        infectious agent (for example, COVID-19) abolition or in vivo        clearance, which can be achieved by the anti-microbial (for        example, anti-viral) pre-vaccination treatment arm of methods as        provided herein;    -   prolonged immunity, which can be achieved by administration of        combined vaccine and intermittent anti-microbial (for example,        anti-viral) treatments as provided herein;    -   lack of novel virus replication in the patient, which can be        achieved by the anti-microbial (for example, anti-viral)        pre-vaccination treatment arm of methods as provided herein;    -   no in vivo infectious agent (for example, virus) mutation in        treated patients, as there is no or substantially no (for        example, 90% to 99% reduction in) replication;    -   no ‘Long Covid Syndrome’, because if there is no infectious        agent (or substantially no infectious agent) remaining in the        patient in vivo, then can be no “Long Covid Syndrome”;    -   no or minimal hospitalization, and no or substantially decreased        number of deaths from Covid-19, because if there is no active in        vivo infection there can be no progression to morbidity or        mortality;    -   inability or substantial decrease in risk for patients treated        using the combination methods as provided herein catch or be        re-infected with any strain nor any mutant strain, where        patients administered methods as provided herein are induced to        have combined immunity (by administration of a vaccine) and an        anti-viral response induced by administration of a drug or drugs        which are viral mutant agonists;    -   eradication of primary viral (for example, COVID-19) infection,        because patients administered methods as provided herein receive        anti-microbial (for example, anti-viral) treatment at the        beginning of therapy; and/or,    -   ideal long-term preventative therapy for the elderly with        senescent immunity by supporting waning antibody levels in the        elderly patient with anti-microbial (for example, anti-viral)        treatment as provided herein; and also in embodiments where        ivermectin is administered, having the added benefit of rosacea        improvement and prevention of scabies in aged-care facilities.

Increasing the dose of the intermittent ivermectin combination increasesits anti-Covid-19 preventative power. In alternative embodiments, thedose is raised from between about 12 mg to about 36 mg, about 48 mg orabout 60 mg, or the dose is raised progressively to 120 mg with few ifany adverse effects. This will create a more prolonged circulatinglevel. This is expected to be close to 100% at 4 weeks, but whencombined with the vaccine could well prevent for up to 6 weeks or more.Hence, creating the possibility of reducing dosing to ×7/year. Given theuse of accompanying anti-viral drugs, even if the vaccine results inlower circulation of neutralizing antibody levels and so immunity, therisk of vaccine breakthrough infection will be minimal if at allpossible. Hence, this combination of anti-viral treatment together withthe vaccine would be ideal therapy for prevention of infection in theelderly population with senescent immune systems.

In alternative embodiments, any vaccine will benefit from practicingmethods as provided herein, particularly the mRNA vaccines, which willbenefit profoundly when combined with an effective anti-viral treatment.

In alternative embodiments, methods as provided herein comprise 1 to 10days of treatment with an ivermectin-based (or ivermectin-comprising)combination, followed by (the first dose of) vaccination, and then every1, 2, 3, 4, 5, 6 or 7 days, and later every 8, 9, 10, 11, 12, 13 or 14days (for example, every 7 days, then every 14 days), and later to 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 or 28 days (for example,every 7 days, then every 14 days, and later every 28 days), administer ahigher dose of ivermectin, for example, 60 mg ivermectin for 4 weekstogether with zinc or a zinc salt, doxycycline, vitamin D and vitamin Cor other appropriate combinations. As long as one continues theanti-viral treatment based on the 60 mg ivermectin regimen, a vaccinatedpatient has both circulating antibodies for many months and cannot catchmutated virus (for example, COVID-19 agents), and therefore “vaccinebreakthrough” will be prevented or substantially decreased and superinfection with mutants will be prevented or substantially decreased.

In alternative embodiments, methods as provided herein, including forexample the ivermectin, zinc or a zinc salt and doxycycline andoptionally also an adjunct therapy (such as for example administering avitamin such as vitamin C or D) is mutant agnostic. In alternativeembodiments, because methods as provided herein, including for examplethe ivermectin combination therapy, functions and works using adifferent mechanism by prevention of replication within a cell, nomutants can affect its activity as has been shown by us in clinicalpractice in California, United States. Hence, the combination of ananti-viral with a vaccine as provided herein may be the best method ofterminating the Covid-19 pandemic.

In alternative embodiments, the vaccination or the inactivated orattenuated causative agent of the infection, or the live, viable orinfectious causative agent of the infection administration may need tobe repeated, for example, repeated at 6 or 12 month (or between about 1(monthly) to 12 month) intervals, but it is of no great importancewhether it is 6 months or 12 months because the second arm or thetherapy as provided herein, the anti-viral arm, is on board to preventany further infection and therefore any further mutation in vivo in thepatient.

In alternative embodiments, even if a mutant or variant strain becomesthe predominant viral agent in a community in the future necessitatingthat the vaccine and/or the inactivated or attenuated causative agent ofthe infection, or the live, viable or infectious causative agent of theinfection be adjusted (or changed) to take in (be specific for) that newmutant or variant strain, the drug combination as provided herein, forexample, the ivermectin, zinc or a zinc salt and doxycycline plusadjunct treatment, can remain the same as it is mutant agnostic. Hence,any vaccine produced by any institution can be supplemented with ananti-viral combination such that no individuals will catch any viralstrains once the individual has begun this program (commenced receivingtreatment regimens as provided herein.

The concept of ‘redundancy’ of treatment is significant here; inmedicine, redundant treatment is one where the medication carries extrapower to cure the condition. In the event that the treatment had to beterminated early (for example, due to an allergy developing) thebuilt-in redundancy still delivers near (substantially) 100% curebecause it was designed to carry extra power. Hence, the combination ofthe anti-viral treatment and vaccination as provided herein carries ahigh level of redundancy and thus can achieve a close to 100% successrate (or a substantially completely successfully cure rate).

Although alternative embodiments of methods as provided herein are bestsuited to prevent and treat a virus such as a coronavirus such as aCovid-19 infection, alternative embodiments have multiple otherapplications. For example, in alternative embodiments, with appropriateantivirals methods as provided herein are used to prevent influenzainfections. In alternative embodiments, provided are methods comprisinga treatment regimen of an influenza (or other viral) vaccine followedlater by antiviral agents intermittently in once a week, 2 weekly, 3weekly, 4 weekly or less frequently spaced intervals to preventinfluenza mutants from re-infecting de novo susceptible elderly patientswith senescent immune system where influenza infection causes the mostmortality. Other exemplary antiviral combinations administeredpracticing methods as provided herein comprise use ofhydroxychloroquine, for example, hydroxychloroquine, azithromycin andzinc or a zinc salt.

In alternative embodiments, provided are methods comprising a treatmentregimen for treating: dengue fever, Zika, HIV, hepatitis C, Eboladisease, SARS, MERS, polio, measles, chickenpox and other viral orretro-viral infections. Where current immunizations may not beadequately effective, the follow-on with intermittent antiviral therapyas provide by methods as provided herein gives extra power for the poorimmune response combined with antivirals to have enough redundancy tomake it clinically effective.

In alternative embodiments, provided are methods comprising use ofantiviral compounds used singly or in multiple combinations, forexample, antiviral compounds are administered singly or in multiplecombinations, for example, before, at the time of vaccination, and/orafter vaccination:

For example, in alternative embodiments, methods provided hereincomprise administering in coordination with (optionally before, at thetime of vaccination, and/or after vaccination of) an anti-microbialvaccine a single drug or a therapeutic combination of drugs, or a singledrug, a pharmaceutical dosage form, a drug delivery device, or a productof manufacture, or the methods can comprise use of: one, two or moreclasses of antiviral drugs used against influenza, such as: M2 proteininhibitors (for example, amantadine and rimantadine); neuraminidaseinhibitors (for example, oseltamivir, zanamivir, peramivir andlaninamivir); favipiravir (also known as T-705 or AVIGAN™, or favilavir,Toyama Chemical, Fujifilm, Japan, or FABIFLU™, GlenmarkPharmaceuticals); a 5- to 6-membered heterocyclic ring such as benzene,naphthalene, furan, benzofuran, pyrrole, pyridine, pyrazole, imidazole,benzimidazole, triazole, tetrazole, oxazole, oxadiazole, 1,3,5-triazine,thiazole, thiophene, benzothiophene, pyrazine, pyridazine, pyrimidine,indole, purine, quinoline or isoquinoline; amantadine; rimantadine;oseltamivir; zanamivir; peramivir; laninamivir; laninamivir octanoatehydrate; arbidol; ribavirin; stachyflin; ingavirin; fludase; aniclosamide compound; an emricasan compound; nitazoxanide; tizoxanide;and/or a compound selected from consisting of teriflunomide,hydroxocobalamin, ensulizole, tenonitrozole, isoliquiritigenin,nitazoxanide, febuxostat, leflunomide, fidofludimus SB-366791, emodin,diphenyl isophthalate, benzoylpas, fenobam, indobufen,2-(2H-Benzotriazol-2-yl)-4-methylphenol, tiaprofenic acid, flufenamicacid, vitamin B12, cinanserin, 5-nitro-2-(3-phenylpropylamino)benzoicacid, veliflapon, thiabendazole, SIB 1893, anethole trithione,naringenin, phenazopyridine, fanetizole, terazosin, diacerein, CAY10505,hesperetin, suprofen, ketorolac tromethamine, piperine, pirarubicin,piraxostat, albendazole oxide, tyrphostin AG 494, genistin, fenbufen,apatinib, RITA, BF-170 hydrochloride, OSI-930, tribromsalan, pifexole,formononetin, ebselen, tranilast, benzylparaben,2-Ethoxylethyl-p-methoxycinnamate, baicalein, nemorubicin, rutaecarpine,2-Methyl-6-(phenylethynyl)pyridine (MPEP), 5,7-dihydroxyflavone, vitaminB12, pipofezine, flurbiprofen axetil, 2-Amino-6-nitrobenzothiazole,nalachite green oxalate, enfenamic acid, fenaminosulf, AS-252424,phenserine, epalrestat, alizarin, dalcetrapib, SN-38, echinomycin,(S)-(+)-camptothecin, BI-2536, 10-hydroxycamptothecin, topotecan,delanzomib, volasertib, ispinesib, paclitaxel, FK-506, emetine, AVN-944,digoxin, vincristine, idarubicin, thapsigargin, lexibulin, ixazomib,cephalomannine, mitoxantrone, MLN-2238, demecolcine, vinorelbine,bardoxolone methyl, cycloheximide, actinomycin D, AZD-7762, PF-184,CHIR-124, cyanein, triptolide, KX-01, PF-477736, epirubicin,mycophenolate (mycophenolic acid), daunorubicin, PIK-75, vindesine,torin-2, floxuridine, Go-6976, OSU-03012, and a prodrug, metabolite, orderivative of any of the foregoing.

In alternative embodiments the following compound (or its isomer, orstereoisomer, or enantiomer, or deuterated version, or bioisostere) isused singly or in various combinations (for example, formulated with, oradministered separately) with other drug such as anti-viral drugsbefore, during or after vaccination or administration of a causativeagent of infection:(1R,2S,5S)-N-[(1S)-1-cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl]-3-[(2S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamideadministered orally or by inhalation (or nasally), for example, asliquid, solid, powder, mist or spray, which can target a protease (suchas the 3CL protease in COVID-19) and optionally has the followingstructure and molecular weight:

This protease inhibitor (PF-07321332, or PAXLOVID™) may be used alonebefore and after the vaccination and/or administration of the attenuatedcausative agent of infection, optionally administered with ritonavir (orNORVIR™) or lopinavir, or with any of the numerous antiviral agents asprovided herein.

In alternative embodiments the following compounds (or their isomers, orstereoisomers, or enantiomer, or bioisostere) can be used singly or invarious combinations:

These compounds (PF-07304814 and/or PF-00835231) (or its isomer, orstereoisomer, or enantiomer, or deuterated version, or bioisostere) maybe used alone before and after the vaccination and/or administration ofthe attenuated causative agent of infection, optionally administeredwith ritonavir (or NORVIR™) or lopinavir, or with any of the numerousantiviral agents as provided herein.

In alternative embodiments, the PF-07321332 (or PAXLOVID™) and ritonavir(or NORVIR™) or lopinavir combination; or the PF-07304814 and/orPF-00835231 and ritonavir (or NORVIR™) or lopinavir combination; or theKALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or LOPINAVIR™ and/orzanamivir (or RELENZA™) combination; is administered separately, ortogether (for example, formulated together) as a tablet, gel, geltab orcapsule, as a powder, in a liquid, in a mist or a spray, or as alozenge. In alternative embodiments, the PE-07321332 (or PAXLOVID™) andritonavir (or NORVIR™) or lopinavir combination; or the PF-07304814and/or PF-00835231 and ritonavir (or NORVIR™) or lopinavir combination;or the KALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or LOPINAVIR™and/or zanamivir (or RELENZA™) combination; is administered before, atthe same time as, and/or after the vaccination.

In alternative embodiments, the PF-07321332 (or PAXLOVID™) and ritonavir(or NORVIR™) or lopinavir combination; or the PF-07304814 and/orPF-00835231 and ritonavir (or NORVIR™) or lopinavir combination; or theKALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or LOPINAVIR™ and/orzanamivir (or RELENZA™) combination; is administered 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13 or 14 or more days before, and/or on the day of,a first dose of the at least one of a plurality of dosages of thevaccine is administered, or a dose of the inactivated, attenuated, orthe live, viable or infectious causative agent of the infection isadministered.

In alternative embodiments, the PF-07321332 (or PAXLOVID™) and ritonavir(or NORVIR™) or lopinavir combination; or the PF-07304814 and/orPF-00835231 and ritonavir (or NORVIR™) or lopinavir combination; or theKALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or LOPINAVIR™ and/orzanamivir (or RELENZA™) combination; is administered 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13 or 14 or more days after a first dose of the atleast one of a plurality of dosages of the vaccine is administered, or adose of the inactivated, attenuated, or the live, viable or infectiouscausative agent of the infection is administered.

In alternative embodiments, the PF-07321332 (or PAXLOVID™) and ritonavir(or NORVIR™) or lopinavir combination; or the PF-07304814 and/orPF-00835231 and ritonavir (or NORVIR™) or lopinavir combination; or theKALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or LOPINAVIR™ and/orzanamivir (or RELENZA™) combination; is administered both before andafter a first dose of the at least one of a plurality of dosages of thevaccine is administered, or a dose of the inactivated, attenuated, orthe live, viable or infectious causative agent of the infection isadministered. Another agent which can be used singly or in combinationbefore and accompanying vaccination is 2-deoxy-D-Glucose (2-DG).

In alternative embodiments, methods as provided herein comprise (orfurther comprise) administering in coordination with (optionally before,at the time of vaccination, and/or after vaccination of) ananti-microbial vaccine (or a dose of the inactivated, attenuated, or thelive, viable or infectious causative agent of the infection) atherapeutic combination of drugs or a single drug, a pharmaceuticaldosage form, a drug delivery device, or a product of manufacture,comprising:

-   -   (a) a thiazolide class drug, optionally nitazoxanide (or        ALINIA™, NIZONIDE™) or tizoxanide (or        2-Hydroxy-N-(5-nitro-2-thiazolyl)benzamide);    -   (b) molnupiravir, optionally co-administered with and/or        formulated with an avermectin class drug (optionally        ivermectin), an antibiotic (optionally doxycycline or        azithromycin) and/or zinc, or co-administered with and/or        formulated with ivermectin, hydroxychloroquine, an antibiotic        (optionally doxycycline or azithromycin) and/or zinc; (c)        opaganib or YELIVA™, or opaganib or YELIVA™ and oral and/or        inhaled or aerosol chloroquine (or ARALEN™), chloroquine        phosphate, chloroquine diphosphate, amodiaquine (or AMDAQUINE™,        AMOBIN™) and/or hydroxychloroquine (optionally, PLAQUENIL™),        wherein optionally each or both of the opaganib and the        chloroquine (or ARALEN™) chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        are in or formulated as a formulation for inhalation, for        example, formulated as an aerosol, spray, mist, liquid or        powder, or each or both are formulated for oral, intramuscular        or intravenous administration,    -   wherein optionally the opaganib is administered at a dosage of        QD (once a day), bid (twice a day) or tid (three times a day) at        a dosage of between about 100 to 600 mg per day or per dosage,        or at about 100, 200, 300, 400, 500 or 600 mg per day or per        dosage,    -   and optionally the opaganib, or YELIVA™ is also administered or        formulated with an antibiotic (optionally azithromycin or        doxycycline), ivermectin (optionally at 12 mg ivermectin,        optionally administered on days 1, 3, 6 and 8),        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc        (optionally zinc sulfate, optionally at (50 mg daily, or any        zinc salt);    -   (d) lopinavir, ritonavir (or NORVIR™) and oseltamivir        (optionally, TAMIFLU™), and/or zanamivir (or RELENZA™);    -   (e) lopinavir combined (formulated) with ritonavir (or NORVIR™),        or KALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or        LOPINAVIR™, and/or zanamivir (or RELENZA™), or lopinavir and        ritonavir separately formulated;    -   (f) lopinavir combined (formulated) with ritonavir (or NORVIR™)        (or KALETRA™, ALTERA™, ALUVIA™, KALMELTREX, LOPIMUNE™ or        LOPINAVIR™), or lopinavir and ritonavir (or NORVIR™), and        oseltamivir (optionally, TAMIFLU™), and/or zanamivir (or        RELENZA™), optionally also with inhaled or aerosol formulations        or versions of chloroquine (or ARALEN™), amodiaquine (or        AMDAQUINE™, AMOBIN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        and/or oral chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) simultaneously;    -   (g) lopinavir, ritonavir (or NORVIR™), amodiaquine (or        AMDAQUINE™, AMOBIN™), chloroquine and oseltamivir (or TAMIFLU™);        wherein optionally the chloroquine comprises inhaled or aerosol        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        and/or oral chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) simultaneously;    -   (H) lopinavir and oseltamivir (optionally, TAMIFLU™), and/or        zanamivir (or RELENZA™);    -   (i) ritonavir (or NORVIR™) and oseltamivir (optionally,        TAMIFLU™), and/or zanamivir (or RELENZA™);    -   (j) remdesivir (optionally, GS-5734™, Gilead Sciences) alone, or        oseltamivir (optionally, TAMIFLU™) and remdesivir (optionally,        GS-5734™, Gilead Sciences), and optionally the remdesivir is an        oral formulation and/or an inhaled or aerosol remdesivir        formulation;    -   (k) oseltamivir (optionally, TAMIFLU™) and efavirenz        (optionally, SUSTIVA™), and/or zanamivir (or RELENZA™);    -   (l) oseltamivir (optionally, TAMIFLU™) and nevirapine (or the        combination efavirenz with emtricitabine and tenofovir, or        ATRIPLA™);    -   (m) oseltamivir (or TAMIFLU™) and amprenavir (optionally,        AGENERASE™);    -   (n) oseltamivir (optionally, TAMIFLU™) and nelfinavir        (optionally, VIRACEPT™);    -   (o) a thiazolide class drug, optionally nitazoxanide (optionally        ALINIA™, NIZONIDE™) or tizoxanide (or        2-hydroxy-N-(5-nitro-2-thiazolyl)benzamide), with or in        combination with any of (a) to (nn), or any drug or drug        combination as provided herein, optionally a thiazolide class        drug, optionally nitazoxanide, with an avermectin class drug        such as ivermectin (optionally STROMECTOL™), moxidectin        (optionally CYDECTIN™, EQUEST™, QUEST™), selamectin (optionally        STRONGHOLD™), a milbemycin (optionally milbemectin, milbemycin        oxime, moxidectin or nemadectin), doramectin (optionally        DECTOMAX™), eprinomectin or abamectin; or a thiazolide class        drug (optionally, nitazoxanide or tizoxanide) and oseltamivir        (or TAMIFLU™),    -   and optionally the thiazolide class drug (optionally,        nitazoxanide or tizoxanide) is formulated or administered with        ribavirin or tribavirin (or COPEGUS™, REBETOL™, or VIRAZOLE™),        and an avermectin class drug such as ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin;    -   (p) plitidepsin (also known as dehydrodidemnin B), or APLIDIN™        (PharmaMar, S. A.);    -   (q) an inhibitor or S-phase kinase-associated protein 2 (SKP2),        or dioscin, or niclosamide, or NICLOCIDE™, FENASAL™, or        PHENASAL™;    -   (r) ritonavir (or NORVIR™), ribavirin or tribavirin (or        COPEGUS™, REBETOL™, or VIRAZOLE™), interferon beta 1b, or a        combination of ribavirin and interferon beta, or a combination        of lopinavir and ritonavir (or NORVIR™) and interferon-beta-1b;    -   (s) a nucleoside analog reverse-transcriptase inhibitor (NRTI)        (optionally abacavir, or ZIAGEN™), acyclovir or aciclovir        (optionally ZOVIRAX™), adefovir (optionally HEPSERA™),        amantadine(optionally GOCOVRI™, SYMADINE™, SYMMETREL™),        rintatolimod (or AMPLIGEN™), amprenavir (optionally,        AGENERASE™), aprepitant (or EMEND™), umifenovir (or ARBIDOL™),        atazanavir (or REYATAZ™), atazanavir (or REYATAZ™), tenofovir, a        combination of efavirenz and emtricitabine and tenofovir (or        ATRIPLA™), balavir, baloxavir marboxil (XOFLUZA™), bepotastine,        bevirimat, bictegravir, a combination of bictegravir and        emtricitabine and tenofovir alafenamide (or BIKTARVY™),        brilacidin, bivalirudin (or BIVALITROBAN™), cidofovir,        caspofungin, lamivudine and zidovudine (optionally, COMBVIR™),        cobicstat, colisitin, cocaine, darunavir, delavirdine, descovy,        didanosine, docosanol, dolutegravir, ecoliever, edoxudine,        efavirenz (optionally, SUSTIVA™), elvitegravir, emtricitabine,        enfuvirtide, foscarnet, fosfonet, galidesivir, ibacitabine,        icatibant, idoxuridine, ifenprodil, imiquimod, imunovir,        indinavir, inosine, an interferon (optionally interferon type I,        interferon type II and/or interferon type III), lamivudine (or        EPIVIR™, ZEFFIX™), lopinavir, loviride, ledipasvir, leronlimab,        maraviroc, methisazone, moroxydine, nelfinavir, nevirapine,        nexavir, nitazoxanide (optionally ALINIA™, NIZONIDE™), norvir, a        nucleoside analogue or derivative (optionally brincidofovir (or        TEMBEXA™), didanosine (or VIDEX™), favipiravir (also known as        T-705 or AVIGAN™, or favilavir, Toyama Chemical, Fujifilm,        Japan, or FABIFLU™, Glenmark Pharmaceuticals), vidarabine,        galidesivir (optionally, BCX4430, IMMUCILLIN-A™), remdesivir        (optionally, GS-5734™, Gilead Sciences), cytarabine,        gemcitabine, emtricitabine, lamivudine, zalcitabine, entecavir,        stavudine, telbivudine, zidovudine, idoxuridine and/or        trifluridine or any combination thereof), oseltamivir (or        TAMIFLU™), peginterferon alfa-2a, penciclovir, peramivir        (optionally, RAPIVAB™), perfenazine, pleconaril, plurifloxacin,        podophyllotoxin, pyramidine, raltegravir, rifampicin, ribavirin        or tribavirin (or COPEGUS™, REBETOL™, or VIRAZOLE™),        rilpivirine, rimantadine, ritonavir (or NORVIR™), saquinavir,        sofosbuvir, stavudine, telaprevir, tegobuv, tenofovir        alafenamide, tenofovir disoproxil, tenofovir, tipranavir,        trifluridine, trizivir, tromantadine, truvada, valaciclovir        (optionally, VALTREX™), valganciclovir, valrubicin, vapreotide,        vicriviroc, vidarabine, viramidine, velpatasvir, vivecon,        zalcitabine, zanamivir (optionally, RELENZA™), zidovudine, an        immunosuppressive drug (optionally tocilizumab or atlizumab, or        ACTEMRA™, or ROACTEMRA™) or any combination thereof;    -   (t) an mucolytic therapy or drug, optionally acetylcysteine,        ambroxol, bromhexine (or BISOLVON™), carbocisteine, erdosteine,        mecysteine or dornase alfa, or an expectorant, optionally        guaifenesin;    -   (u) a viral, or a coronavirus or a COVID-19, protease inhibitor,        optionally ASC09 (CAS registry no. 1000287-05-7) (Janssen        Research and Development, LLC), ritonavir (or NORVIR™) or ASC09        and ritonavir (or NORVIR™), or a JAK1/2 inhibitor (optionally        baricitinib), optionally compound 11r (University of Lubeck,        Germany, see optionally, Zhang et al J. Med Chem 2020, Feb. 11,        2020), or darunavir, cobicistat or darunavir and cobicistat;    -   (v) an angiotensin-converting enzyme 2 (ACE2) inhibitor,        optionally to block the site of viral spike protein interaction        for anti-SARS-CoV-2 infection control;    -   (w) an anti-vascular endothelial growth factor (VEGF)        (optionally VEGF-A) drug or antibody, optionally bevacizumab;    -   (x) a protease inhibitor, optionally danoprevir, optionally a        serine protease inhibitor, optionally camostat or narlaprevir        (optionally ARLANSA™);    -   (y) anti-PD-1 checkpoint inhibitor, optionally camrelizumab;    -   (z) a compound or antibody capable of binding complement factor        C5 and blocking membrane attack complex formation, optionally        eculizumab;    -   (aa) a cathepsin inhibitor, optionally a cathepsin K, B or L        inhibitor, optionally relacatib;    -   (bb) thalidomide, or thalidomide and glucocorticoid (optionally        ciclesonide (or ALVESCO™, OMNARIS™, OMNIAIR™, ZETONNA™ or        ALVESCO™)) (optionally low-dose glucocorticoid), or and        thalidomide and celecoxib;    -   (cc) an antibacterial antibiotic or a macrolide drug,    -   wherein optionally the macrolide drug comprises azithromycin,        optionally dosaged at between about 50 mg to about 2000 mg per        dose or per day (optionally, ZITHROMAX™, or AZITHROCIN™,        optionally an oral extended- or delayed-release formulation of        azithromycin, or ZMAX™), clarithromycin (optionally, BIAXIN™),        erythromycin (optionally, ERYTHROCIN™), or fidaxomicin        (optionally, DIFICID™ or DIFICLIR™), troleandomycin (optionally,        TEKMISIN™), tylosin (optionally, TYLOCINE™ or TYLAN™),        solithromycin (optionally, SOLITHERA™), oleandomycin (or        SIGMAMYCINE™), midecamycin, roxithromycin, kitasamycin or        turimycin, josamycin, carbomycin or magnamycin, and/or        spiramycin,    -   and optionally the antibacterial antibiotic comprises a        tetracycline class drug, a glycylcycline or a fluorocycline        class drug, or an analogue thereof, and optionally the        tetracycline, glycylcycline or fluorocycline drug or analogue        thereof comprises or is: tetracycline or SUMYCIN™;        chlortetracycline or AUREOMYCIN™; oxytetracycline;        demeclocycline or DECLOMYCIN™, DECLOSTATIN™, LEDERMYCIN™,        BIOTERCICLIN™, DEGANOL™, DETECLO™, DETRAVIS™, MECICLIN™,        MEXOCINE™, CLORTETRIN™; lymecycline; meclocycline; metacycline;        minocycline or MINOCIN™; rolitetracycline; doxycycline, or        DORYX™, DOXYHEXA™, DOXYLIN™; tigecycline or TYGACIL™;        eravacycline or XERAVA™; sarecycline or SEYSARA™, omadacycline        or NUZYRA™; or any combination thereof, and optionally the        antibacterial antibiotic or macrolide drug, optionally        azithromycin (or ZMAX™), is administered in combination with,        and/or is combined with, chloroquine (or ARALEN™), amodiaquine        (or AMDAQUINE™, AMOBIN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™),        and the combination is administered commencing on the first,        second, third, fourth, fifth, sixth, seventh, eighth, ninth        and/or tenth day of therapy, or is administered for 1, 2, 3, 4,        5, 6, 7, 8, 9, 10 or up to 20 or more days, or for between about        1 to 21 days or longer, or is administered until within 1, 2, 3,        4, 5, 6, 7, 8, 9, 10 or up to 20 or more days of ending the        therapy for treating, preventing, ameliorating, slowing the        progress of, decreasing the severity of or preventing the        coronavirus infection,    -   and optionally the chloroquine (or ARALEN™), chloroquine        phosphate, amodiaquine (or AMDAQUINE™, AMOBIN™), chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        is administered the entire length of the treatment but the        azithromycin, optionally dosaged at between about 50 mg to about        2000 mg per dose or per day (optionally, ZITHROMAX™, or        AZITHROCIN™, optionally an oral extended-release formulation of        azithromycin, or ZMAX™) administration is halted or ceased after        two, three, four, five or six days after treatment is commenced,        and optionally the azithromycin administration is replaced by a        tetracycline class drug, and optionally the tetracycline class        drug comprises doxycycline, or DORYX™, DOXYHEXA™, DOXYLIN™        administration,    -   and optionally the antibacterial antibiotic, optionally        azithromycin (optionally, ZITHROMAX™, or AZITHROCIN™, optionally        dosaged at between about 50 mg to about 2000 mg per dose or per        day,    -   and optionally an oral extended-release formulation of        azithromycin, or ZMAX™), is administered or formulated with an        avermectin class drug such as ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin, and/or cholecalciferol (vitamin D3) or calcifediol,    -   and optionally the antibacterial antibiotic comprises an        antimycobacterial drug, and optionally the antimycobacterial        drug comprises clofazimine (optionally LAMPRENE™);    -   (dd) an avermectin class drug such as ivermectin (optionally        STROMECTOL™, SOOLANTRA™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin, optionally dosaged and/or administered at about 5        microgram/kg to about 1 gram (g) per day, optionally formulated        or administered at about 1 to 10, 12, 15, 20, 30, 40, 50, 60,        70, 80, 100, 120, 140, 160, 180, 200, 220 or 240 mg per day, or        between about 1 to 240 mg per day, or between about 3 to 240 mg        per day,    -   optionally formulated or administered with an antibiotic        (optionally azithromycin, minocycline, amoxicillin, niclosamide,        nitazoxanide, hydroxychloroquine or doxycycline, and optionally        the doxycycline is at between about 25 to 600 mg per dose or per        day, or at about 100 mg per dose or per day, and optionally the        azithromycin is at between about 50 mg to 2000 mg per dose or        per day), optionally as a single or a divided dose, and        optionally formulated and administered as an inhalant or a mist        (optionally using a nebulizer, nasal spray or equivalent),        optionally formulated as an aerosol, spray, mist, liquid or        powder, optionally formulated as an aerosol, spray, mist, liquid        or powder,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is formulated with and/or administered with        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        with or without zinc (optionally a zinc sulphate, acetate,        gluconate or picolinate or any zinc salt), and optionally this        combination is administered weekly, or every two week, or one        every 5 to 28 days, as a prophylactic,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is administered alone in the morning (AM), and an        antibiotic (optionally doxycycline) and/or a chloroquine        (optionally, ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        is administered in the afternoon and/or evening,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is administered alone for 1, 2, 3, 4, 5, 6, 7, 8,        9, 10 or up to 20 or more days, followed by administration of an        antibiotic (optionally doxycycline) for a corresponding period        of days, and optionally repeating the cycle of dosaging,    -   and optionally the avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin is formulated or administered with:        -   (i) at least one antibiotic (wherein optionally the            antibiotic is doxycycline(optionally, DORYX™, DOXYHEXA™,            DOXYLIN™) (optionally formulated or administered at a dosage            of between about 25 mg to 600 mg per dose or per day), or            azithromycin (optionally, ZITHROMAX™, or AZITHROCIN™,            optionally dosaged at between about 50 mg to about 2000 mg            per dose or per day, optionally an oral extended-release            formulation of azithromycin, or ZMAX™) (optionally            formulated or administered at a dosage of between an about            50 mg to 2000 mg);        -   (ii) chloroquine (or ARALEN™), chloroquine phosphate,            chloroquine diphosphate and/or hydroxychloroquine            (optionally, PLAQUENIL™) (optionally formulated or            administered at a dosage of between an about 10 mg to 2000            mg per day);        -   (iii) a zinc (optionally a zinc sulphate, acetate, gluconate            or picolinate or any zinc salt) optionally formulated or            administered at a dosage of between about 1 mg to 250 mg;            and/or        -   (iv) at least one vitamin, and optionally the at least one            vitamin comprises: vitamin C optionally formulated or            administered at a dosage of between about 500 to 5000            units (U) per dose, and/or Vitamin D (or cholecalciferol)            optionally formulated or administered at a dosage of between            about 3,000 to 100,000 units per day, or between about            10,000 to 50,000 units a day,        -   and optionally the avermectin class drug such as ivermectin            (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,            EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a            milbemycin (optionally milbemectin, milbemycin oxime,            moxidectin or nemadectin), doramectin (optionally            DECTOMAX™), eprinomectin or abamectin is administered or            formulated alone or in combination with any of the above (i)            to (iv) (for example, at least one antibiotic, chloroquine            (or ARALEN™), chloroquine phosphate, chloroquine diphosphate            and/or hydroxychloroquine (optionally, PLAQUENIL™), zinc or            any zinc salt and/or at least one vitamin are formulated            (and administered) as oral formulations (for example, as            tablets, capsules, gels or geltabs), injectable            formulations, powders (for example, for inhalation or for            addition to an ingestible liquid) or liquids (for example,            for ingestion, infusion or injection);    -   (ee) chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) alone or with (or formulated with) or in combination        with any of (a) to (bb), or chloroquine, chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) and oseltamivir (or TAMIFLU™);    -   (ff) chloroquine (optionally, ARALEN™), chloroquine phosphate,        alone or with:        -   (i) an avermectin class drug such as ivermectin (optionally            STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,            QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin            (optionally milbemectin, milbemycin oxime, moxidectin or            nemadectin), doramectin (optionally DECTOMAX™), eprinomectin            or abamectin, optionally at a dosage of between about 3 to            340 mg per day, or about 6 mg to 60 mg, or about 10 mg to 80            mg dosages, or about 12 to 50 mg dosages;        -   (ii) vitamin D, vitamin D2 (or ergocalciferol), vitamin D3            (or cholecalciferol) optionally at a dosage of between about            3,000 to 100,000 units per day, or between about 10,000 to            50,000 units a day, and/or        -   (iii) with (i) and (ii) and zinc (optionally a zinc            sulphate, acetate, gluconate or picolinate or any zinc salt)            optionally at a dosage of between about 1 mg to 250 mg,            or (iv) the combination of (iii) also with a tetracycline            class drug, wherein optionally the tetracycline class drug            comprises doxycycline, or DORYX™, DOXYHEXA™, DOXYLIN™,            optionally dosages at between about 25 mg to 600 mg per day            or per dose, optionally between about 100 mg to 500 mg, or a            between about 200 mg to 400 mg per dose or per day;    -   (gg) colchicine, or COLCRYS™, MITIGARE™, optionally administered        or dosaged at between about 0.5 mg to 20 mg, or about 1 mg to 15        mg, or about 3 mg to mg, or about 4 mg to 6 mg, per day for a        period of between about 7 and 21 days, or about 14 days, and        optionally also administered or formulated with an antibiotic        (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily);    -   (hh) a corticosteroid or glucocorticoid class drug such as        ciclesonide (or ALVESCO™, OMNARIS™, OMNIAIR™, ZETONNA™ or        ALVESCO™) budesonide (optionally RHINOCORT™ or PULMICORT™),        prednisolone (or ORAPRED™), methyl-prednisolone, prednisone (or        DELTASONE™ or ORASONE™) or hydrocortisone (or CORTEF™), wherein        optionally the corticosteroid or glucocorticoid class drug        (optionally ciclesonide) is inhaled,    -   or a selective estrogen receptor modulator (SERM), or toremifene        (or FARESTON™), or clomifene or clomiphene (or CLOMID™,        SEROPHENE™) wherein optionally the SERM is inhaled;    -   and optionally the corticosteroid class drug (for example        budesonide) is administered by inhalation, for example, in a        nebulized form, for example, between about 1 mg to 12 mg per day        of budesonide is administered by inhalation, or between about 6        to 80 mg per day of prednisolone is administered orally, or        between about 6 to 100 mg per day of prednisone is administered        orally, or between about 30 to 400 mg per day of hydrocortisone        is administered orally,    -   and optionally the corticosteroid class drug is formulated as a        powder or for administration in an inhaler or by nasal spray, or        for rectal administration,    -   and optionally the corticosteroid class drug (for example,        budesonide) is administered together with or in combination with        10 mg to 80 mg, an antibiotic (optionally azithromycin or a        tetracycline class drug,    -   wherein optionally the tetracycline class drug comprises        doxycycline, or DORYX™, DOXYHEXA™, DOXYLIN™), zinc or any zinc        salt and/or a vitamin (optionally vitamin D or calcifediol, D2        (or ergocalciferol), D3 (or cholecalciferol), C, E, B12, B6);    -   (ii) an anti-androgen drug, and optionally the anti-androgen        drug is bicalutamide, optionally CASODEX™, or dutasteride (or        AVODART™),        -   and optionally the anti-androgen drug is a nonsteroidal            anti-androgen (NSAA) or an androgen receptor (AR)            antagonist, and optionally the NSAA or AR antagonist            comprises proxalutamide (or its developmental name GT-0918)            (Suzhou Kintor Pharmaceuticals, Inc., a subsidiary of Kintor            Pharmaceutical Limited), or flutamide (or niftolide, or            EULEXIN™), or bicalutamide (or CASODEX™) or enzalutamide (or            XTANDI™),        -   and optionally the anti-androgen drug comprises a            5α-reductase inhibitor, and optionally the 5α-reductase            inhibitor comprises finasteride (or PROSCAR™, PROPECIA™, or            FINIDE™)        -   and optionally the anti-androgen drug, or NSAA, or            proxalutamide or bicalutamide, is administered together with            or in combination with an avermectin class drug such as            ivermectin (optionally STROMECTOL™), moxidectin (optionally            CYDECTIN™, EQUEST™, QUEST™), selamectin (optionally            STRONGHOLD™), a milbemycin (optionally milbemectin,            milbemycin oxime, eprinomectin or abamectin;        -   and optionally the anti-androgen drug, or NSAA, or            bicalutamide, proxalutamide, flutamide or niftolide,            bicalutamide, enzalutamide or dutasteride, is administered            at dosages of about 50 to 100 mg optionally administered            once, twice (BID), three times (TID) or four times a day, or            is administered at dosages of about 50 to 100 mg per day,        -   and optionally the anti-androgen drug, or NSAA, or            bicalutamide, proxalutamide, flutamide or niftolide,            bicalutamide, enzalutamide or dutasteride, is administered            with an avermectin class drug, or ivermectin, optionally            also administered with hydroxychloroquine, zinc and/or a            vitamin (optionally vitamin D (optionally vitamin D2, or            ergocalciferol, or Vitamin D3 or cholecalciferol, optionally            administered at about 1000 to 4000 ugm/day) or vitamin C, B            or A;    -   and optionally bicalutamide is administered together with or in        combination with an avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin,    -   and optionally bicalutamide is administered together with or in        combination with an avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin;    -   (jj) a hydrocortisone or cortisol (optionally CORTEF™,        SOLUCORTEF™), optionally hydrocortisone sodium succinate or        hydrocortisone acetate or dexamethasome (optionally DEXTENZA™,        OZURDEX™, NEOFORDEX™);    -   (kk) an alpha-ketoamide (α-ketoamide), wherein optionally the        alpha-ketoamide is a structure as described by Zhang et al, J.        Med. Chem. 2020, 63, 9, 4562-4578, or Meng et al Chem.        Sci. (2019) vol. 10, pg 5156 (optionally the structure KAM-2),    -   and optionally the alpha-ketoamide is formulated or administered        as an inhalant or a powder or mist, and optionally formulated or        administered with (optionally as an inhalant): an avermectin        class drug such as ivermectin (optionally STROMECTOL™),        moxidectin (optionally CYDECTIN™, EQUEST™, QUEST™), selamectin        (optionally STRONGHOLD™), a milbemycin (optionally milbemectin,        milbemycin oxime, moxidectin or nemadectin), doramectin        (optionally DECTOMAX™), eprinomectin or abamectin; an antibiotic        (optionally azithromycin or a tetracycline class drug, wherein        optionally the tetracycline class drug comprises doxycycline, or        DORYX™, DOXYHEXA™, DOXYLIN™); chloroquine (or ARALEN™),        chloroquine phosphate, chloroquine diphosphate and/or        hydroxychloroquine (optionally, PLAQUENIL™); zinc or any zinc        salt; remdesivir (optionally, GS-5734™, Gilead Sciences);        oseltamivir (or TAMIFLU™); and/or, hydrocortisone; or, any        combination thereof;    -   (ll) a compound, drug or formulation that decreases stomach acid        production or decreases stomach pH, wherein optionally the        compound, drug or formulation comprises famotidine, or PEPCID™,        and optionally the famotidine is administered at a dosage of        between about 10 to 60 mg per day, or between about 20 to 40 mg        per day, and optionally the famotidine is administered is        administered with: an avermectin class drug such as ivermectin        (optionally STROMECTOL™), moxidectin (optionally CYDECTIN™,        EQUEST™, QUEST™), selamectin (optionally STRONGHOLD™), a        milbemycin (optionally milbemectin, milbemycin oxime, moxidectin        or nemadectin), doramectin (optionally DECTOMAX™), eprinomectin        or abamectin, and/or a tetracycline tetracycline class drug, and        optionally the tetracycline class drug comprises doxycycline, or        DORYX™, DOXYHEXA™, DOXYLIN™;    -   (mm) a dendrimer, optionally astodrimer sodium (Starpharma,        Melbourne, Australia);    -   (nn) an antihistamine class drug such as azelastine, or        ASTELIN™, OPTIVAR™, ALLERGODIL™, brompheniramine, fexofenadine        or ALLEGRA™ pheniramine or AVIL™, or chlorpheniramine;    -   (oo) a selective serotonin reuptake inhibitor (SSRI) class drug,        optionally fluvoxamine, or LUVOX™, FAVERIN™, FLUVOXIN™;    -   (pp) a nicotinic antagonist, a dopamine agonist or a        noncompetitive N-Methyl-d-aspartic acid or N-Methyl-d-aspartate        (NMDA) antagonist, wherein optionally the nicotinic antagonist,        dopamine agonist or noncompetitive NMDA antagonist is        1-adamantylamine or amantadine, or GOCOVRI™, SYMADINE™,        SYMMETREL™, optionally administered or dosaged at between about        50 mg to 150 mg, or about 100 mg, per day for a period of        between about 7 and 21 days, or about 14 days, and optionally        the nicotinic antagonist, dopamine agonist or noncompetitive        NMDA antagonist is also administered or formulated with an        antibiotic (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily),        and optionally the amantadine is formulated or administered at        100 mg per day for the first two days of treatment, which        optionally can then be elevated to 100 mg twice daily,        optionally for the next 10 days;    -   (qq) an immunosuppressive drug, wherein optionally the        immunosuppressive drug comprises tocilizumab or atlizumab, or        ACTEMRA™, or ROACTEMRA™, or a calcineurin inhibitor (CNI),        wherein the CNI comprises ciclosporin (or cyclosporine or        cyclosporin), or NEORAL™, or SANDIMMUNE™, or tacrolimus, or        PROTOPIC™, or PROGRAF™, and optionally the immunosuppressive        drug is also administered or formulated with an antibiotic        (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily),    -   and optionally the calcineurin inhibitor (CNI), wherein the CNI        comprises ciclosporin (or cyclosporine or cyclosporin) is        formulated combination of CNI (optionally cyclosporine) at a        dose of 3 mg/kg (180 mg daily) together with 12 mg ivermectin        once, and optionally also plus zinc 50 mg base and doxycycline        100 mg bid, optionally all for 10 days;    -   (rr) a protein kinase inhibitor, wherein optionally the protein        kinase inhibitor is a p38 mitogen-activated protein kinase        inhibitor, or ralimetinib, and optionally the protein kinase        inhibitor is also administered or formulated with an antibiotic        (optionally azithromycin or doxycycline), ivermectin,        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily);    -   (ss) an anti-inflammatory therapy or at least one        anti-inflammatory therapy drug, wherein optionally the        anti-inflammatory therapy or drug comprises: a sphingosine        kinase-2 (SK2) selective inhibitor (optionally, opaganib        (optionally, YELIVA™), sirolimus, a JAK1/2/TYK2 inhibitor        (optionally ruxolitinib), an anti-CD47 mAb (optionally        meplazumab), a cyclooxygenase (COX) (optionally, COX2)        inhibitor, a glucocorticoid (optionally a synthetic        glucocorticoid, hydrocortisone, dexamethasone (or DEXTENZA™,        OZURDEX™, or NEOFORDEX™) or cortisol, or CORTEF™), plitidepsin        or dehydrodidemnin B, or APLIDIN™, or a nonsteroidal        anti-inflammatory drug (NSAID), wherein optionally the NSAID        comprises indomethacin (or indomethacin) or INDOCID™ or        INDOCIN™, or naproxen, or NAPROSYN™ or ALEVE™, or a        cyclooxygenase inhibitor, or a COX-1 or an COX-2 inhibitor, or        aspirin, or ibuprofen or ADVIL™, MOTRIN™ or NUROFEN™, or        celecoxib or CELEBREX™, or parecoxib or DYNASTAT™, or etoricoxib        or ARCOXIA™,    -   and optionally the anti-inflammatory therapy or        anti-inflammatory therapy drug is also administered or        formulated with an antibiotic (optionally azithromycin or        doxycycline), ivermectin, hydroxychloroquine (optionally,        PLAQUENIL™) and/or zinc or any zinc salt (optionally zinc        sulfate, optionally at (50 mg daily),    -   and optionally opaganib, or YELIVA™, or opaganib, or YELIVA™        administered or formulated together with an oral and/or inhaled        or aerosol chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™),    -   and optionally the opaganib or YELIVA™ is formulated or        administered at a dosage of QD (once a day), bid (twice a day)        or tid (three times a day) at a dosage of between about 100 to        600 mg per day or per dosage, or at about 100, 200, 300, 400,        500 or 600 mg per day or per dosage,    -   and optionally the opaganib, or YELIVA™ is also administered or        formulated with an antibiotic (optionally azithromycin or        doxycycline), ivermectin (optionally at 12 mg ivermectin,        optionally administered on days 1, 3, 6 and 8),        hydroxychloroquine (optionally, PLAQUENIL™) and/or zinc or any        zinc salt (optionally zinc sulfate, optionally at (50 mg daily);    -   (tt) a calcium channel blocker, or verapamil (or ISOPTIN™,        CALAN™), or a voltage gated potassium (KCNH2) channel or a        voltage gated calcium channel (CACNA2D2) blocker, or amiodarone        (or CORDARONE™, NEXTERONE™);    -   (uu) suramin, or ANTRYPOL™, BAYER 305™, or GERMANIN™    -   (vv) a peroxisome proliferator-activated receptor (PPAR)        agonist, wherein optionally the PPAR agonist comprises        fenofibrate, or TRICOR™, FENOBRAT™, FENOGLIDE™, or LIPOFEN™, or        a combination of fenofibrate and simvastatin, or CHOLIB™,        optionally the PPAR agonist comprises a combination of        fenofibrate and pravastatin, or PRAVAFENIX™, or the PPAR agonist        comprises bezafibrate, or BEZALIP™, or combination of        bezafibrate and chenodeoxycholic acid, or HEPACONDA™, or        aluminium clofibrate, or alfibrate, or ciprofibrate, or        clinofibrate or LIPOCLIN™, or clofibrate or ATROMID-S™, or        clofibride, or gemfibrozil or LOPID™, or ronifibrate, or        simfibrate or CHOLESOLVIN™, or any combination thereof,    -   (ww) a synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or a prodrug of N4-hydroxycytidine,        optionally molnuvpiravir (Merck), or favipiravir (also known as        T-705 or AVIGAN™, or favilavir, Toyama Chemical, Fujifilm,        Japan, or FABIFLU™, Glenmark Pharmaceuticals),    -   wherein the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is given as between        about 10 mg to 3 gm per dose, or between about 10 mg to 3 gm per        day, or can be dosed either as a single dose or given one, two,        three or four times a day, or is administered at 200 to 800 mg        twice daily, or 200, 400, 600 or 800 mg twice daily, or at 200        to 800 mg three times a day, or at 200, 400, 600 or 800 mg three        times a day, or is administered at 200 to 800 mg three times a        day for between about 2 to 15 days, or for about 2, 3, 4, 5, 6,        7, 8, 9, 10, 11 or 12 days, and optionally when combined with        other drugs a lower dosage is used, optionally administered at        100 or 200 mg three times a day for between about 5 to 15 days,        or for about 7, 8, 9, 10, 11 or 12 days,    -   and optionally the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is administered with an        avermectin class drug (optionally ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin),    -   and optionally the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is administered with an        avermectin class drug (optionally ivermectin) with an        antibiotic, and optionally the antibiotic comprises        azithromycin, minocycline, amoxicillin, niclosamide,        nitazoxanide, hydroxychloroquine or doxycycline), and optionally        the synthetic nucleoside analog or derivative, avermectin class        drug, and antibiotic are administered together or as separate        formulations, and optionally are administered every one, two,        three, four or five weeks for between about one month and one        year or more;    -   and optionally molnuvpiravir, ivermectin and hydroxychloroquine        are administered together or as separate formulations, and        optionally are administered every one, two, three, four or five        weeks for between about one month and one year or more;    -   and optionally the synthetic nucleoside analog or derivative        (optionally N4-hydroxycytidine, or the prodrug of        N4-hydroxycytidine, optionally molnuvpiravir or favipiravir),        and antibiotic (optionally doxycycline or hydroxychloroquine) is        administered with zinc (optionally a zinc sulphate, acetate,        gluconate or picolinate, or zinc oxide nanoparticles, optionally        at a dosage of between about 1 mg to 250 mg, or about 50 mg per        day) and/or a vitamin, optionally vitamin C or D),    -   and optionally the synthetic nucleoside analog or derivative, or        N4-hydroxycytidine, or the prodrug of N4-hydroxycytidine,        optionally molnuvpiravir or favipiravir, is administered with an        antibiotic (optionally the antibiotic comprises azithromycin,        minocycline, amoxicillin, niclosamide, nitazoxanide,        hydroxychloroquine or doxycycline), optionally also administered        with zinc (optionally a zinc sulphate, acetate, gluconate or        picolinate, or zinc oxide nanoparticles, optionally at a dosage        of between about 1 mg to 250 mg, or about 50 mg per day) and/or        a vitamin, optionally vitamin C or D,    -   and optionally the anti-androgen drug, or NSAA, or bicalutamide,        proxalutamide, flutamide or niftolide, bicalutamide,        enzalutamide or dutasteride, is administered with colchicine (or        COLCRYS™, MITIGARE™), and optionally also zinc and/or a vitamin        (optionally vitamin D (optionally vitamin D2, or ergocalciferol,        or Vitamin D3 or cholecalciferol, optionally administered at        about 1000 to 4000 ugm/day), or vitamin C, B or A),    -   and optionally the anti-androgen drug, or NSAA, or bicalutamide,        proxalutamide, flutamide or niftolide, bicalutamide,        enzalutamide or dutasteride, is administered with an antibiotic        (optionally azithromycin or doxycycline), and optionally also        zinc and/or a vitamin (optionally vitamin D (optionally vitamin        D2, or ergocalciferol, or Vitamin D3 or cholecalciferol,        optionally administered at about 1000 to 4000 ugm/day), or        vitamin C, B or A), and optionally also with hydroxychloroquine;    -   (xx) an anti-malarial drug, wherein optionally the anti-malarial        drug comprises mefloquine (or LARIAM™, MEPHAQUIN™, or MEFLIAM™)    -   (yy) an antisera or an antibody or antibody or vaccine therapy        for treating, preventing or ameliorating a microbial or a viral        infection (optionally a coronavirus infection, optionally a        COVID-19 infection) or a microbial infection (optionally a        protozoan, helminthiasis, insect and/or parasitic infection),        and optionally the antibody comprises a monoclonal antibody, and        optionally the monoclonal antibody comprises sotrovimab        (GlaxoSmithKline and Vir Biotechnology), or casirivimab,        imdevimab or casirivimab and imdevimab (REGEN-COV™) (Regeneron),        or bamlanivimab oretesevimab or bamlanivimab and etesevimab        (Junshi Biosciences), or tocilizumab or ACTEMRA™ or ROACTEMRA™        (Hoffmann-La Roche), and optionally the vaccine comprises        tozinamera or COMIRNATY™ (Pfizer), or elasomeran or SPIKEVAX™        (Moderna), or SPUTNIK V™ or Gam-COVID-Vac (Gamaleya Research        Institute), or AZD1222 or COVISHIELD™ or VAXZEVRIA™        (Oxford-AstraZeneca),    -   and optionally the antibody or antibody therapy comprises or is        contained in a convalescent sera or plasma, and/or    -   (zz) any combination of (a) to (yy), and optionally any of these        combinations is administered very 2, 3, 4, 5, 6, 7, 8, 9 or 10        or more days for between about 1 month and one year or more,    -   and optionally any one or several or all of (a) to (zz) with an        (or formulated with or formulated as an) inhaled or aerosol        formulation such as a powder, spray or a mist or aerosol, and/or        formulated with or formulated as an oral, intramuscular (IM) or        intravenous (IV) formulation, wherein optionally both the        inhaled (or aerosol) and the oral, IV and/or IM formulations are        administered simultaneously or sequentially,    -   and optionally the inhaled or aerosol formulation comprises        chloroquine (or ARALEN™), chloroquine phosphate, chloroquine        diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™)        and/or oral chloroquine (or ARALEN™), chloroquine phosphate,        chloroquine diphosphate and/or hydroxychloroquine (optionally,        PLAQUENIL™) administered simultaneously or overlapping,    -   and optionally the inhaled or aerosol formulation comprises an        avermectin class drug such as ivermectin (optionally        STROMECTOL™), moxidectin (optionally CYDECTIN™, EQUEST™,        QUEST™), selamectin (optionally STRONGHOLD™), a milbemycin        (optionally milbemectin, milbemycin oxime, moxidectin or        nemadectin), doramectin (optionally DECTOMAX™), eprinomectin or        abamectin,    -   and optionally any one or several or all of (a) to (zz), or any        therapeutic combination of drugs or a drug, or a pharmaceutical        dosage form as provided herein, are administered orally,        intramuscularly, subcutaneously, topically, by use of an enema,        intravaginally, or intravenously, or administration is by        subcutaneous administration, sublingual administration,        inhalation or by aerosol (optionally by inhalation of a liquid,        an aerosol, a spray, a mist or a powder), by absorbable patch,        by use of an implant, or by use of an enema or a suppository.

In alternative embodiments, the anti-viral drug or medication, oranti-microbial drug, is or comprises: molnupiravir, efavirenz(optionally, SUSTIVA™), tenofovir, emtricitabine and tenofovir,nevirapine (or the combination efavirenz with emtricitabine andtenofovir, or ATRIPLA™), amprenavir (optionally, AGENERASE™), nelfinavir(optionally, VIRACEPT™) and/or remdesivir (optionally, GS-5734™, GileadSciences), a viral RNA-dependent RNA polymerase inhibitor, optionallygalidesivir, a nucleoside analog reverse-transcriptase inhibitor (NRTI)(optionally abacavir, or ZIAGEN™)

-   -   and optionally the anti-viral drug or medication is or comprises        an anti-retroviral drug or drug combination, and optionally the        anti-retroviral drug or drug combination comprises: darunavir        and cobicistat (optionally, REZOLSTA™ or PREZCOBIX™); atazanavir        and cobicistat (or EVOTAZ™); abacavir, lamivudine and        dolutegravir (TRIUMEQ™); tenofovir (or disoproxil or        emtricitabine) and elvitegravir and cobicistat (optionally,        STRIBILD™); tenofovir (or disoproxil or emtricitabine) and        elvitegravir and cobicistat (COMPLERA™ or EVIPLERA™);        molnupiravir, efavirenz (optionally, SUSTIVA™), emtricitabine        and tenofovir (ATRIPLA); lamivudine, nevirapine and stavudine        (optionally, TRIOMUNE™); atazanavir and cobicistat (optionally,        EVOTAZ™); lamivudine and raltegravir (optionally, DUTREBIS™);        lamivudine and dolutegravir (or DOVATO™); doravirine, lamivudine        and tenofovir (optionally, DELSTRIGO™); or lamivudine,        zidovudine and nevirapine (optionally, CUOVIR-N™);    -   and optionally the additional anti-viral drug or medication, or        anti-microbial drug, is formulated with the chloroquine        (optionally, ARALEN™), chloroquine phosphate, chloroquine        diphosphate, hydroxychloroquine (optionally, PLAQUENIL™),        lopinavir, ritonavir (or NORVIR™) and/or oseltamivir or is        formulated separately from the chloroquine (optionally,        ARALEN™), chloroquine phosphate, chloroquine diphosphate,        hydroxychloroquine (optionally, PLAQUENIL™), lopinavir,        ritonavir (or NORVIR™) and/or oseltamivir,    -   and optionally the anti-viral drug or medication, or        anti-microbial drug, or palliative agent comprises or further        comprises: magnesium (Mg, optionally administer        intravenously (IV) to maintain a blood concentration of between        about 2.0 and 2.4 mmol/l); zinc or any zinc salt (optionally a        zinc sulphate, acetate, gluconate or picolinate, optionally        administered at about 75 to 100 mg/day or at a dosage of between        about 1 mg to 250 mg); at least one vitamin, wherein optionally        the at least one vitamin comprises vitamin K, vitamin D or        calcifediol (optionally D2 (or ergocalciferol) or Vitamin D3 or        cholecalciferol), optionally administered at about 1000 to 4000        ugm/day), vitamin B6 (or pyridoxine), vitamin B12, vitamin E,        and/or vitamin C (optionally administered at 500 mg bid); a        flavonoid, plant flavonol or quercetin optionally administered        at between about 250 to 500 mg bid; atorvastatin, or LIPITOR™,        SORTIS™ (optionally administered at between about 40 mg/day to        80 mg/day); or, melatonin, or CIRCADIN™, SLENYTO™ (optionally        between about 6 to 12 mg a day, optionally, at night), any of        which are optionally given enterally or parenterally.        Anti-Clotting or Blood Thinning Agents

In alternative embodiments for practicing methods as provided herein, toaddress the possibility of blood clotting, whether the blood clotting iscaused by the infectious agent, the administered inactivated orattenuated causative agent of the infection, or the live, viable orinfectious causative agent of the infection, and/or the vaccine or forany another reason, an anti-clotting or anti-coagulant or blood thinningdrug or agent is also administered, for example, before and/or at thecommencement of the vaccination, and optionally is continued for betweenabout 1 to 2 or 1 to 6 weeks after the vaccination, or for the durationof the anti-microbial drug treatment though administration of a secondor booster vaccination, and/or for between about 1 to 2 weeks afteradministration of the second or booster vaccination.

In alternative embodiments, the anti-clotting agent or anti-coagulant orblood thinning drug or agent comprises aspirin, for example betweenabout 100 mg to 500 mg aspirin administered (for example, in themorning, or AM, or MANE) for 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or14 or more days commencing on the day of the vaccination or commencingone or two days before the vaccination day.

In alternative embodiments, antiplatelet drugs that can be used includeclopidogrel (PLAVIX™), prasugrel (EFFIENT™) and ticagrelor (BRILINTA™).

In alternative embodiments, the anti-clotting or anti-coagulant agent orblood thinning drug or agent comprises: heparin; warfarin (orCOUMADIN™); a coumarin; phenprocoumon (or MARCUMAR™); rivaroxaban(XARELTO™); dabigatran (PRADAXA™); apixaban (ELIQUIS™); edoxaban(LIXIANA™) and/or betrixaban (BEVYXXA™)

Vaccines

In alternative embodiments, provided are methods for treating,ameliorating, decreasing the chances of having any adverse effects from,decreasing the severity of adverse effects from, or preventing aninfection by administration of an antibiotic and/or an anti-viral drugsand a vaccine directed to a causative agent of the infection, and/or aninactivated or attenuated causative agent of the infection, or a live,viable or infectious causative agent of the infection.

In alternative embodiments, vaccines used to practice methods asprovided herein are directed to an exterior-expressed protein of apathogen, for example, where the pathogen is a bacteria or a virus, forexample, the exterior-expressed protein comprises a spike protein of avirus, for example, a spike protein of a coronavirus, for example, aCovid-19 spike protein.

In alternative embodiments, vaccines used to practice methods asprovided herein are formulated and administered using any formulations,protocols or techniques known in the art, for example, pharmaceuticalformulations or vaccines as provided herein can be administered aspeptides, or can be administered in the form of nucleic acids thatencode the immunogenic peptides or proteins. In alternative embodiments,vaccines used to practice methods as provided herein comprise orally andintra-nasally administered vaccines.

In alternative embodiments, vaccines used to practice methods asprovided herein comprise administration of inactivated pathogen, forexample, an inactivated virus (optionally an inactivated whole or entirepathogen (or virus) or substantially a whole or entire pathogen (orvirus), for example, an inactivated coronavirus, for example, andinactivated COVID-19 virus, for example, as manufactured by Valneva,France), Sinopharm, or Bharat Biotech. In alternative embodiments, thepathogen (or virus) is inactivated using a chemical, for example, abeta-propiolactone (BPL) or equivalent, or any means used to inactivatea viruses for a vaccine. This type of inactivation can preserve thestructure of the pathogen (for example, viral) proteins, as they wouldoccur in nature. This means the immune system will be presented withsomething similar to what occurs naturally and mount a strong immuneresponse. In alternative embodiments, after being inactivated, thevaccine (or, the inactivated pathogen, or virus) is highly purified. Inalternative embodiments, an adjuvant (or any immune stimulant) is addedor co-administered to induce a boosted or strong immune response.

In alternative embodiments, vaccines used to practice methods asprovided herein are DNA vaccine or RNA vaccines. For example, inalternative embodiments the immunogen-encoding nucleic acid can be a DNAencoding one or more immunogenic peptides or proteins, and the DNA canbe carried in an expression vehicle such as a viral vector, for examplean adenovirus vector such as an Ad5 or adeno-associated vector (AAV). Inalternative embodiments, recombinant adenoviruses as used in vaccines asprovided herein can be as described in U.S. patent application no. US20200399323 A1, which describes for example recombinant adenovirusesincluding a deletion in or of the E1 region or any deletion that rendersthe virus replication-defective, for example, the replication-defectivevirus can include a deletion in one or more of the E1, E3, and/or E4regions; or, can be as described in U.S. patent application no. US20190382793 A1, which described how to make recombinant adenoviruses forgene therapy.

In alternative embodiments, the immunogen-encoding nucleic acid can bean RNA, for example, mRNA, which can be formulated in a lipidformulation or a liposome and injected for example intramuscularly (IM),for example using formulations and methods as described in U.S. patentapplication no. US 20210046173 A1, which describes delivering to asubject (for example, via intramuscular administration) an immunogeniccomposition that comprises a RNA (for example, mRNA) that comprises anopen reading frame (ORF) that comprises (or consists of, or consistsessentially of) an immunogenic or antigenic sequence as provided herein;wherein optionally the RNA (or the DNA-carrying expression vehicle) isformulated in a liposome, or a lipid nanoparticle (LNP), ornanoliposome, that comprises: non-cationic lipids comprise a mixture ofcholesterol and DSPC, or a PEG-lipid, or PEG-modified lipid, or LNP, oran ionizable cationic lipid; or a mixture of(13Z,16Z)-N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine, cholesterol,DSPC, and PEG-2000 DMG. In alternative embodiments, the PEG-lipid is1,2-Dimyristoyl-sn-glycerol methoxypolyethylene glycol (PEG-DMG),PEG-disteryl glycerol (PEG-DSG), PEG-dipalmetoleyl, PEG-dioleyl,PEG-distearyl, PEG-diacylglycamide (PEG-DAG), PEG-dipalmitoylphosphatidylethanolamine (PEG-DPPE), orPEG-1,2-dimyristyloxlpropyl-3-amine (PEG-c-DMA), or, the PEG-lipid isPEG coupled to dimyristoylglycerol (PEG-DMG). In alternativeembodiments, the LNP comprises 20-99.8 mole % ionizable cationic lipids,0.1-65 mole % non-cationic lipids, and 0.1-20 mole % PEG-lipid. Inalternative embodiments, the LNP comprises an ionizable cationic lipidselected from the group consisting of(2S)-1-({6-[(3))-cholest-5-en-3-yloxy]hexyl}oxy)-N,N-dimethyl-3-[(9Z)-octadec-9-en-1-yloxy]propan-2-amine;(13Z,16Z)-N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine; andN,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]heptadecan-8-amine; or apharmaceutically acceptable salt thereof, or a stereoisomer of any ofthe foregoing. In alternative embodiments, the PEG modified lipidcomprises a PEG-modified phosphatidylethanolamine, a PEG-modifiedphosphatidic acid, a PEG-modified ceramide, a PEG-modified dialkylamine,a PEG-modified diacylglycerol, a PEG-modified dialkylglycerol, andmixtures thereof. In alternative embodiments, the ionizable cationiclipid comprises: 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane(DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate(DLin-MC3-DMA), di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319),(13Z,16Z)-N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine,(12Z,15Z)-N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine, andN,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]heptadecan-8-amine. In oneembodiment, the lipid is(13Z,16Z)-N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine orN,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]heptadecan-8-amine, each ofwhich are described in PCT/US2011/052328, the entire contents of whichare hereby incorporated by reference. In some embodiments, anon-cationic lipid of the disclosure comprises1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC),1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE),1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC),1,2-dimyristoyl-sn-gly cero-phosphocholine (DMPC),1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC),1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC),1,2-diundecanoyl-sn-glycero-phosphocholine (DUPC),1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC),1,2-di-O-octadecenyl-sn-glycero-3-phosphocholine (18:0 Diether PC),1-oleoyl-2 cholesterylhemisuccinoyl-sn-glycero-3-phosphocholine(OChemsPC), 1-hexadecyl-sn-glycero-3-phosphocholine (C16 Lyso PC),1,2-dilinolenoyl-sn-glycero-3-phosphocholine,1,2-diarachidonoyl-sn-glycero-3-phosphocholine,1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine,1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (ME 16.0 PE),1,2-distearoyl-sn-glycero-3-phosphoethanolamine,1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine,1,2-dilinolenoyl-sn-glycero-3-phosphoethanolamine,1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine,1,2-didocosahexaenoyl-sn-glycero-3-phosphoethanolamine,1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG),sphingomyelin, or mixtures thereof.

Attenuated, or Live, Viable or Infectious Causative Agent of theInfection

In alternative embodiments, provided are methods for treating,ameliorating, decreasing the chances of having any adverse effects from,decreasing the severity of adverse effects from, or preventing aninfection, comprising administering to a subject or an individual inneed thereof:

-   -   (a) at least one antibiotic and/or anti-viral drug capable of        killing a causative agent of the infection, or completely or        partially inhibiting the ability of the causative agent of the        infection to replicate or become infectious or cause pathology        in the subject or the individual in need thereof; and,    -   (b) (i) at least one dose of a vaccine directed to the causative        agent of the infection upon entry into the vaccinated subject or        individual in need thereof,    -   wherein the vaccine is capable of initiating an immune response        in the individual that can substantially or partially kill or        neutralize a causative agent of the infection, or the vaccine        can completely, substantially or partially inhibit the ability        of the causative agent of the infection to replicate, or be        infectious, or cause pathology, in the subject or the individual        in need thereof, and/or    -   (ii) an inactivated or attenuated causative agent of the        infection, or a live, viable or infectious causative agent of        the infection, wherein optionally the live causative agent of        the infection is a completely or partially attenuated version of        the causative agent,    -   wherein at least one dosage of the at least one antibiotic        and/or anti-viral drug is administered 1, 2, 3, 4, 5, 6, 7, 8,        9, 10, 11, 12, 13 or 14 or more days before, or on the day of, a        first dose of the at least one of a plurality of dosages of the        vaccine is administered, or a dose of the inactivated,        attenuated causative agent of the infection, or the live, viable        or infectious causative agent of the infection.

In alternative embodiments, the causative agent of the infection is orcomprises a bacteria, protozoan or a virus, or

-   -   the causative agent of the infection is or comprises the        causative agent of:        -   a viral infection, optionally a coronavirus, a virus that            causes a common cold, an influenza virus (optionally an            influenza A, B or C), a hepatitis virus, a rous sarcoma            virus (RSV), a Paramyxoviridae or measles virus, a            Paramyxovirus or mumps virus, a Herpes simplex virus (HSV),            a Cytomegalovirus (CMV), a Rubivirus or rubella virus, an            Enterovirus, a viral meningitis, a rhinovirus, a human            immunodeficiency virus (HIV), a varicella-zoster or            chickenpox virus, an Orthopoxvirus or variola or smallpox            virus, an Epstein-Barr virus (EBV), an Adenovirus, a            Hantavirus, a Flaviviridae or Dengue virus, a Zika virus, or            a chikungunya virus infection,        -   a coronavirus infection, optionally a COVID-19 or a COVID-19            variant infection, or a Middle East respiratory syndrome            virus (MERS-CoV) infection;        -   malaria caused by a parasite of the genus Plasmodium            (optionally P. vivax, P. falciparum, P. malariae, P. ovale,            or P. knowlesi);        -   dengue fever or dengue shock syndrome caused by a virus of            the Flaviviridae family or a dengue virus;        -   a Flaviviridae family virus infection or a hepatitis or a            hepatocellular carcinoma associated with viral hepatitis            caused by a virus of the Flaviviridae family or a virus of            the genus Hepacivirus or Hepacivirus C virus or hepatitis C;        -   filariasis, leprosy or streptocerciasis or an infection            caused by a parasite of the superfamily Filarioidea            (optionally Brugia malayi, Brugia timori, Wuchereria            bancrofti, Loa loa, Mansonella streptocerca, Mansonella            ozzardi, or Mansonella perstans);        -   leprosy or an infection caused by a parasite of the genus            Mycobacterium (optionally M. leprae or M. lepromatosis);        -   river blindness or onchocerciasis caused by a parasitic worm            or a parasite of the genus Onchocerca (optionally O.            volvulus);        -   a hookworm or a roundworm infection caused by a parasite of            the genus Ancylostoma (optionally A. duodenale or A.            ceylanicum) or Necator (optionally N. americanus);        -   trichuriasis or a whipworm infection caused by a parasite of            the genus Trichuris (optionally T. trichiura); roundworm or            an Ascaris infection that is caused by Ascaris lumbricoides;        -   scabies or a mite-carried infection caused by the parasite            of the genus Sarcoptes (optionally S. scabiei);        -   typhus or an infection caused by a lice or a parasite of the            order Phthiraptera (optionally Pediculus humanus capitis);        -   enterobiasis or an infection caused by a pinworm or a            parasite of the genus Enterobius (optionally E.            vermicularis); and/or        -   pulicosis or an infection caused by a flea or an insect of            the order Siphonaptera or of the genus Pulex (optionally P.            irritans).

In alternative embodiments, the inactivated or attenuated causativeagent of the infection, or the live, viable or infectious causativeagent of the infection is administered orally or by inhalation.Alternatively, the inactivated or attenuated causative agent of theinfection, or the live, viable or infectious causative agent of theinfection can be administered by inclusion of the live, viable orinfectious causative agent of the infection in a liquid (optionally tobe administered as a drink or in drops such as nasal drops), a tablet, alozenge, an aerosol, spray, or mist formulation that is inhaled oradministered nasally or orally (optionally, by a puffer of a nebulizer),or the inactivated or attenuated causative agent of the infection, orthe live, viable or infectious causative agent of the infection isformulated in a liquid (optionally the liquid is a sterile saline)solution which is ingested or gargled by the individual in need thereof.

In alternative embodiments, the source of the inactivated or attenuatedcausative agent of the infection, or the administered live, viable orinfectious causative agent of the infection can be from an infectedindividual, such as a human patient, a domesticated, wild or lab animal,or from a lab-grown culture. In alternative embodiments, the source ofthe administered inactivated or attenuated causative agent of theinfection, or the live, viable or infectious causative agent of theinfection is from swab or sputum or other biological samples from aninfected individual or patient. In alternative embodiments, the sputumor other biological sample from an infected individual or patient isdiluted in a water or a saline prior to administrations.

In alternative embodiments, the administered inactivated or attenuatedcausative agent of the infection, or the live, viable or infectiouscausative agent of the infection is attenuated (in other words, itsability to cause pathogenesis is completely, substantially or partiallyabrogated or diminished, for example is genetically deleted ordiminished by genomic engineering).

In alternative embodiments, to generate an attenuated (e.g., completedinactivated) version of a causative agent of the infection to beadministered, the causative agent of the infection is passaged multipletimes in culture (or in vitro) or in an animal (or in vivo), wherevariants from each passage are selected for a phenotype and/or genotypethat has diminished ability to cause pathogenesis.

In alternative embodiments, to generate an attenuated (e.g., completedinactivated, completely non-infectious) version of a causative agent ofthe infection to be administered, the causative agent of the infectionis treated with radiation and/or a chemical. For example, the chemicalcan be iodine (for example, povidone-iodine or PVP-1, also known asiodopovidone, or BETADINE™, WOKADINE™, PYODINE™), or any complex ofpolyvinylpyrrolidone and iodine, alcohol and/or formalin.

In alternative embodiments, the causative agent of the infection isrendered inactive, or non-infectious, by exposing the causative agent ofthe infection to iodine or povidone-iodine or PVP-1 (povidone is alsoknown as polyvinylpyrrolidone (PVP), or1-vinyl-2-pyrrolidinon-polymere), also known as iodopovidone, orBETADINE™, WOKADINE™, PYODINE™, as in the production of nasodine(Firebrick Pharma Pty Ltd, Australia). Povidone-iodine is a chemicalcomplex of povidone, hydrogen iodide, and elemental iodine or triiodide(I³⁻); and it contains 10% povidone, with total iodine species equaling10,000 ppm or 1% total titratable iodine, and it works by releasingiodine which results in the death of a range of microorganisms. Inalternative embodiment, the causative agent of infection is mixed withPVP-I and water, ethyl alcohol, isopropyl alcohol, polyethylene glycolor glycerol.

In alternative embodiments, the attenuated, or inactivated, causativeagent, or live causative agent, is administered with an adjuvant, wherethe adjuvant can comprise: an inorganic compound such as alum (e.g.,potassium alum), an aluminium salt or aluminium hydroxide, aluminiumphosphate, or calcium phosphate; an oil such as paraffin oil, propolisor Adjuvant 65; a bacterial product such as killed bacteria of the genusBordetella or Mycobacterium or of the species Bordetella pertussis orMycobacterium bovis; a plant saponin or soybean extract; a cytokine suchas interleukin-1 (IL-1), IL-2 or IL-12; Freund's complete adjuvant orFreund's incomplete adjuvant; and/or, an organic compound such assqualene.

In alternative embodiments, the attenuated, or inactivated, causativeagent, or live causative agent, with or without an adjuvant, isadministered by nasal spray or nebulizer, or orally for example bylozenge, tablet, capsule or geltab, or by subcutaneous injection, orintramuscularly (IM), or by suppository, or via an implant.

In alternative embodiments, attenuated viruses are made using a liveattenuated codon-pair-deoptimized virus approach as described forexample in Wang et al PNAS, Jul. 20, 2021, vol. 18 (29) e2102775118; oras described by Coleman et al. Science 320, 1784-1787 (2008), or Chenget al J. Virol. 89, 3523-3533 (2015), or Gonçalves-Carneiro, mBio 12,e02238-20 (2021).

For example, methods as provided herein comprise administration of theWang et al, COVI-VAC™ attenuated virus, which was developed by recodinga segment of the viral spike protein with synonymous suboptimal codonpairs (codon-pair deoptimization), thereby introducing 283 silent(point) mutations. As described by Wang et al, synthetic highlyattenuated live vaccine is generated by recoding portions of the WTSARS-CoV-2 genome according to the SAVE algorithm of codon-pair biasdeoptimization. In addition, the furin cleavage site within the spikeprotein was deleted from the viral genome for added safety of thevaccine strain. Except for the furin cleavage site deletion, theCOVI-VAC and parental SARS-CoV-2 amino acid sequences are identical,ensuring that all viral proteins can engage with the host immune systemof vaccine recipients. Attenuated viruses can be generated from viralgenomes recover from WT SARS-CoV-2, strain USA-WA1/2020 (GenBankaccession No. MN985325).

In alternative embodiments, the inactivated or attenuated causativeagent of the infection, or the live, viable or infectious causativeagent of the infection, is administered in unit dosages of between about10 to 50, or 1 to 20, trillion infectious units (or particles, ifattenuated), or between about one infectious unit to 10, 20 or 30billion infection units (or particles, if attenuated).

Hand-Held or Portable Devices

In alternative embodiments, provided are portable, for example,hand-held (or worn around the neck), medical devices, for example, aninhaler, ionizer, asthma puffer or nebulizer, capable of administeringan inhalation product comprising a composition or formulation asprovided herein or as described herein, for example, an inactivated orattenuated agent of the infection, or a live, viable or infectiouscausative agent of the infection with or without a vaccine or with orwithout an adjuvant, or with or without an antimicrobial drug, forexample, as described herein.

In alternative embodiments, a portable, for example, hand-held, medicaldevice, for example, inhaler, asthma puffer or nebulizer, as providedherein can administer ionized air or air comprising generated electronsand/or negatively-charged oxygen ions and/or positively-charged ions.

In alternative embodiments, a portable or hand-held medical device asprovided herein comprises a cassette, packette, interchangeable disk(for example, for holding a powder) or reservoir (optionally arefillable reservoir) in or on the product of manufacture, or aremovable cassette or packette, interchangeable disk (for example, forholding a powder) that can be inserted into a slot or port on theproduct of manufacture, or a separate reservoir or container operativelylinked or joined to the product of manufacture, that comprises a vaccineor or live or attenuated causative agent of invention or a formulationor a medication, for inhalation as provided herein for delivery to auser.

In alternative embodiments, provided is a modified hairdryer-typemedical device capable of having an adjustable temperature, adjustableair intake; a provision (or receptacle) for insertion of adrug-containing cassette (optionally providing or delivering acombination of medications, or the live or attenuated causative agentsand/or a vaccine as provided herein); and/or warm-to hot airavailability (optionally with temperature control) to inhibit viral andbacterial growth.

In alternative embodiments, a medical device as provided herein forinhalation delivery of a live or attenuated causative agent of infectionand/or a vaccine as provided herein drug or a medication or combinationsthereof to a user is fabricated as a meter-dose inhaler (MDI) (eitheropen or closed mouth MDI), which can comprise a pressurized canister ofthe drug or medication in a plastic case with a mouthpiece, and aholding chamber having a plastic tube with a mouthpiece, a valve tocontrol mist delivery and a soft sealed end to hold the MDI; the holdingchamber can assist delivery of the drug or medication to the nose and/orlungs, for example, as an AEROCHAMBER™ device.

In alternative embodiments, the inhaler or nebulizer is breathactivated, for example, as an REDIHALER™ device.

In alternative embodiments, a medical device as provided herein forinhalation delivery of a live or attenuated causative agent of infectionand/or a vaccine or a drug or a medication or combinations thereof to auser is fabricated a dry powder inhaler (such as a dry powder diskinhaler, for example, as a DISKUS™ device), optionally having a dosecounter window so user can see how many doses are left), for example,where the powder is dose dispensed by (using) a disposable, refillableor replaceable cassette, packette or disk; and the dry powder dispensingcan be breath activated, for example, as an AEROLIZER™, FLEXHALER™,PRESSAIR™, DISKUS™, HANDIHALER™, TWISTHALER™, ELLIPTA™, NEOHALER™,RESPICLICK™, ROTAHALER™ or TUBUHALER™ device.

In alternative embodiments, a medical device as provided herein forinhalation delivery of a live or attenuated causative agent ofinfection, or a vaccine or a drug or a medication or combinationsthereof, to a user is fabricated a nebulizer or soft mist inhaler, whichcan comprise a nebulizer delivery system comprising a nebulizer (forexample, a small plastic bowl with a screw-top lid) and a source forcompressed air to generate a mist comprising the drug or medication,which also can be dose dispensed using a disposable, refillable orreplaceable cassette, packette or disk.

In alternative embodiments, a medical device as provided herein forinhalation delivery of a live or attenuated causative agent ofinfection, or a vaccine or drug or a medication or combinations thereofto a user is fabricated a dry powder inhaler (such as a dry powder diskinhaler, for example, as a DISKUS™ device), optionally having a dosecounter window so user can see how many doses are left), for example,where the powder is dose dispensed by (using) a disposable, refillableor replaceable cassette, packette or disk; and the dry powder dispensingcan be breath activated, for example, as an AEROLIZER™, FLEXHALER™,PRESSAIR™, DISKUS™, HANDIHALER™, TWISTHALER™, ELLIPTA™, NEOHALER™,RESPICLICK™, ROTAHALER™ or TUBUHALER™ device.

Products of Manufacture and Kits

Provided are products of manufacture and kits for practicing methods asprovided herein; and optionally, products of manufacture and kits canfurther comprise instructions for practicing methods as provided herein.

Any of the above aspects and embodiments can be combined with any otheraspect or embodiment as disclosed here in the Summary, Figures and/orDetailed Description sections.

As used in this specification and the claims, the singular forms “a,”“an” and “the” include plural referents unless the context clearlydictates otherwise.

Unless specifically stated or obvious from context, as used herein, theterm “or” is understood to be inclusive and covers both “or” and “and”.

Unless specifically stated or obvious from context, as used herein, theterm “about” is understood as within a range of normal tolerance in theart, for example within 2 standard deviations of the mean. About (use ofthe term “about”) can be understood as within 20%, 19%, 18%, 17%, 16%,15%, 14%, 13%, 12% 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%,0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise clear fromthe context, all numerical values provided herein are modified by theterm “about.”

Unless specifically stated or obvious from context, as used herein, theterms “substantially all”, “substantially most of”, “substantially allof” or “majority of” encompass at least about 75%, 80%, 85%, 90%, 91%,92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99.5%, or more of a referencedamount of a composition.

The entirety of each patent, patent application, publication anddocument referenced herein hereby is incorporated by reference. Citationof the above patents, patent applications, publications and documents isnot an admission that any of the foregoing is pertinent prior art, nordoes it constitute any admission as to the contents or date of thesepublications or documents. Incorporation by reference of thesedocuments, standing alone, should not be construed as an assertion oradmission that any portion of the contents of any document is consideredto be essential material for satisfying any national or regionalstatutory disclosure requirement for patent applications.Notwithstanding, the right is reserved for relying upon any of suchdocuments, where appropriate, for providing material deemed essential tothe claimed subject matter by an examining authority or court.

Modifications may be made to the foregoing without departing from thebasic aspects of the invention. Although the invention has beendescribed in substantial detail with reference to one or more specificembodiments, those of ordinary skill in the art will recognize thatchanges may be made to the embodiments specifically disclosed in thisapplication, and yet these modifications and improvements are within thescope and spirit of the invention. The invention illustrativelydescribed herein suitably may be practiced in the absence of anyelement(s) not specifically disclosed herein. Thus, for example, in eachinstance herein any of the terms “comprising”, “consisting essentiallyof”, and “consisting of” may be replaced with either of the other twoterms. Thus, the terms and expressions which have been employed are usedas terms of description and not of limitation, equivalents of thefeatures shown and described, or portions thereof, are not excluded, andit is recognized that various modifications are possible within thescope of the invention.

A number of embodiments of the invention have been described.Nevertheless, it can be understood that various modifications may bemade without departing from the spirit and scope of the invention.Accordingly, other embodiments are within the scope of the followingclaims.

What is claimed is:
 1. A method for treating, ameliorating, decreasingthe chances of having any adverse effects from, decreasing the severityof adverse effects from a coronavirus infection, comprisingadministering to a subject or an individual in need thereof: (a) ananti-viral drug combination capable of killing a causative agent of theinfection, or inhibiting the ability of the causative agent of theinfection to replicate or become infectious or cause pathology in thesubject or the individual in need thereof wherein the anti-viral drugcombination comprises: (i)1R,2S5S)-N-[(1S)-1-cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl]-3-[(2S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide,or a compound having the following structure and molecular weight:

(ii) ritonavir, and (iii) a drug combination comprising (1) ivermectin,(2) doxycycline, and (3) zinc; and, (b) a live, inactivated orattenuated causative agent of the infection, wherein at least one dosageof the anti-viral drug combination is administered 1 or more daysbefore, or on the day of, and/or is administered 1 or more days after, afirst dose of the live, inactivated or attenuated causative agent of theinfection.
 2. The method of claim 1, wherein the doxycycline is dosagedat between about 50 mg to about 2000 mg per dose or per day.
 3. Themethod of claim 1, wherein the zinc comprises or is formulated as: zincsulphate, zinc acetate, zinc gluconate or zinc picolinate or a zincsalt.
 4. The method of claim 1, wherein at least one day before, or onthe day of administration of, or at least one day after the first doseof the live, inactivated or attenuated causative agent of the infectionis given, the individual in need thereof is administered the anti-viraldrug combination.
 5. The method of claim 4, wherein the individual inneed thereof is administered the anti-viral drug combination on day zeroor the day of administration of the live, inactivated or attenuatedcausative agent of the infection, or day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13 or 14, or one, two, three and/or four weeks afteradministration of the first dosage of the attenuated and/or the live,inactivated or attenuated causative agent of the infection.
 6. Themethod of claim 1, further comprising administering to a subject or anindividual in need thereof: (a) a booster, (b) at least one secondbooster or follow-up administration of: at least one dosage of the live,inactivated or attenuated and causative agent of the infection, is givenbetween about 1 week to one year, or between about two weeks to 9months, or between about three weeks to 8 months, or between about onemonth to 7 months, or about 3, 4, 5, or 6 months, after the firstadministration of the live, inactivated or attenuated causative agent ofthe infection, or (c) a third booster, wherein on day zero, or at leastone day, or about two days, after, administration of a second or anadditional booster dose of the live, inactivated or attenuated causativeagent of the infection, is given, and the individual in need thereof isadministered an additional dose of the anti-viral drug combination. 7.The method of claim 6, wherein the individual in need thereof isadministered an additional dose of the anti-viral drug combination onday 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 afteradministration of the second or additional or booster dose of the live,inactivated or attenuated causative agent of the infection.
 8. Themethod of claim 7, wherein the anti-viral drug combination is repeatedlyadministered if plasma ivermectin is not detectable after a first orsubsequent administration for about every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, or 14 or more days for one or 2, 3, 4, 5, or 6 weeks untilplasma ivermectin is detectable.
 9. The method of claim 1, wherein theanti-viral drug combination, and/or the live, inactivated or attenuatedcausative agent of the infection, is administered or formulated: (a)orally or by inhalation, or is administered by inclusion in a liquid;(b) as a drink or in drops, wherein optionally the drops comprise nasaldrops; (c) in a mist formulation; (d) as a tablet, a capsule, a gel, ageltab, a powder, a lozenge, an aerosol, spray, or mist formulation thatis inhaled or administered nasally or orally; (e) by or using a pufferor a nebulizer; or (f) in a liquid, wherein optionally the liquid is asterile saline solution which is ingested or gargled by the individualin need thereof.
 10. The method of claim 1, wherein the live,inactivated attenuated causative agent of the infection is administeredin unit dosages of between about 10 to 50 trillion infectious units orparticles, or between about one infectious unit or particle to 10, 20 or30 billion infection units or particles.
 11. The method of claim 1,wherein: (a) after the first administration of the live, inactivated orattenuated causative agent of the infection, IgM, IgG and/or IgA levelsin the individual in need thereof is tested and measured qualitativelyand/or quantitatively, and if levels of the measured IgM, IgG and/or IgAare low, a second or additional dosage or administration of the live,inactivated or attenuated causative agent of the infection is given, or(b) after the first administration of the live, inactivated orattenuated and/or the live, viable or infectious causative agent of theinfection levels of the measured IgM, IgG and/or IgA are measured atbetween about 7 to 21 days, or at 14 and 20 days.
 12. The method ofclaim 1, wherein the individual in need thereof is a human or an animal,or a domestic, farm or zoo animal.
 13. The method of claim 1, whereinthe (i)1R,2S,5S)-N-[(1S)-1-cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl]-3-[(2S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide,or a compound having the following structure and molecular weight:

(ii) ritonavir, and (iii) a drug combination comprising (1) ivermectin,(2) doxycycline, and (3) zinc, are formulated together, or separately,or are formulated together or separately in or as a liquid, or areadministered as a drink or in drops, or are administered as nasal dropsor in a mist, a tablet, a capsule, a gel, a geltab, a powder, a lozenge,an aerosol or spray.
 14. The method of claim 1, wherein the anti-viraldrug combination is formulated in or as a pharmaceutical dosage form, oris formulated to be administered orally, intramuscularly,subcutaneously, topically, by use of an enema, intravaginally, orintravenously, or is formulated for subcutaneous administration,sublingual administration, inhalation or by aerosol, by inhalation of aliquid, an aerosol, a spray, a mist or a powder, or is formulated in anabsorbable patch, an implant, or an enema or a suppository.
 15. Themethod of claim 1, wherein the: (a)1R,2S,5S)-N-[(1S)-1-cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl]-3-[(2S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide,or a compound having the following structure and molecular weight:

(b) ritonavir, and (c) a drug combination comprising (1) ivermectin, (2)doxycycline, and (3) zinc, is or are administered: (a) at a dosage of QD(once a day), bid (twice a day) or tid (three times a day) at a dosageof between about 100 to 600 mg per day or per dosage, or at about 100,200, 300, 400, 500 or 600 mg per day or per dosage, or (b) at a dosageof between about 10 mg to 3 gm per dose, or between about 10 mg to 3 gmper day, or 12 mg or 3 mg/kg orally twice daily, or 125 mg orally twicedaily or 520 mg/130 mg solution twice per day, or is administered withefavirenz, fosamprenavir, nelfinavir, or nevirapine, or (c) is dosedeither as a single dose or given one, two, three or four times a day, or(d) at 200 to 800 mg twice daily, or 200, 400, 600 or 800 mg twicedaily, or at 200 to 800 mg three times a day, or at 200, 400, 600 or 800mg three times a day, or is administered at 200 to 800 mg three times aday for between about 2 to 15 days, or for about 2, 3, 4, 5, 6, 7, 8, 9,10, 11 or 12 days, (e) for pediatric patients dosage at 16 mg or 4 mg/kgorally twice daily, or (f) when combined with other drugs a lowerdosage, or is administered at 100 or 200 mg three times a day forbetween about 5 to 15 days, or for about 7, 8, 9, 10, 11 or 12 days. 16.The method of claim 1, wherein the coronavirus infection is or comprisesa COVID-19 or a COVID-19 variant infection.
 17. The method of claim 1,wherein at least one dosage of the anti-viral drug combination isadministered 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 or more daysbefore, or on the day of, and/or is administered 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13 or 14 or more days after, a first dose of the live,inactivated or attenuated causative agent of the infection.